Scholars@Duke
Madan Mohan Kwatra

Madan Mohan Kwatra

Associate Professor in Anesthesiology
Anesthesiology
madan.kwatra@duke.edu
Box 3094 Med Ctr, Durham, NC 27710
146 Sands Bldg, Durham, NC 27710

Selected Publications

Spatial Mass Cytometry-Based Single-Cell Imaging Reveals a Disrupted Epithelial-Immune Axis in Prurigo Nodularis.

Journal Article J Invest Dermatol · November 2024 Prurigo nodularis (PN) is a chronic, inflammatory skin condition that disproportionately affects African Americans and features intensely pruritic, hyperkeratotic nodules on the extremities and trunk. PN is understudied compared with other inflammatory ski ... Full text Link to item Cite

Immune stimulus exposure as a trigger for the development of chronic pruritus and circulating blood type 2 inflammation.

Journal Article JAAD Int · September 2024 BACKGROUND: Chronic pruritus (CP) is a poorly characterized condition associated with intense pruritus without a primary skin eruption. This condition tends to emerge more commonly in older adults, and there is limited research on triggering factors. OBJEC ... Full text Link to item Cite

Plasma metabolomic profiling reveals a novel circulating biomarker signature in chronic pruritus of unknown origin.

Journal Article Sci Rep · July 29, 2024 Chronic pruritus of unknown origin (CPUO) is characterized by chronic itch for 6 weeks or greater without an identifiable primary cause. Studies are needed to investigate circulating blood biomarkers to elucidate disease pathogenesis. The objective of this ... Full text Link to item Cite

Single-Cell RNA Sequencing Reveals Dysregulated POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis.

Journal Article J Invest Dermatol · July 2024 Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. We performed single-cell transcriptomic profiling of 28,695 lesional and nonlesional PN cells. Lesional PN has increased dysregulated fibrobla ... Full text Link to item Cite

Efficacy and Safety of Abrocitinib in Prurigo Nodularis and Chronic Pruritus of Unknown Origin: A Nonrandomized Controlled Trial.

Journal Article JAMA Dermatol · July 1, 2024 IMPORTANCE: Prurigo nodularis (PN) and chronic pruritus of unknown origin (CPUO) are chronic pruritic diseases that dramatically impair quality of life, but therapeutic options are limited. Abrocitinib, a Janus kinase 1 inhibitor, represents a promising th ... Full text Link to item Cite

Dupilumab Therapy Modulates Circulating Inflammatory Mediators in Patients with Prurigo Nodularis.

Journal Article JID Innov · July 2024 Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intense pruritus and skin nodules. Beyond the skin, PN involves circulating blood inflammation that may contribute to systemic disease comorbidities. Dupilumab was recently appr ... Full text Link to item Cite

Comprehensive plasma cytokine and chemokine profiling in prurigo nodularis reveals endotypes in Type 2 inflammation.

Journal Article Sci Rep · April 6, 2024 Prurigo nodularis (PN) is a chronic inflammatory skin disease that is associated with variability in peripheral blood eosinophil levels and response to T-helper 2 targeted therapies (Th2). Our objective was to determine whether circulating immune profiles ... Full text Link to item Cite

Transcriptomic and proteomic analysis of tumor suppressive effects of GZ17-6.02 against mycosis fungoides.

Journal Article Sci Rep · January 23, 2024 Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). Despite having a wide variety of therapeutic agents available for the treatment of MF, patients often suffer from a significant decrease in quality of life and rarely achie ... Full text Link to item Cite

Integrated plasma metabolomic and cytokine analysis reveals a distinct immunometabolic signature in atopic dermatitis.

Journal Article Front Immunol · 2024 IMPORTANCE: Disease models for atopic dermatitis (AD) have primarily focused on understanding underlying environmental, immunologic, and genetic etiologies. However, the role of metabolic mechanisms in AD remains understudied. OBJECTIVE: To investigate the ... Full text Link to item Cite

A Polygenic Risk Score for Predicting Racial and Genetic Susceptibility to Prurigo Nodularis.

Journal Article J Invest Dermatol · December 2023 Prurigo nodularis (PN) is an understudied inflammatory skin disease characterized by pruritic, hyperkeratotic nodules. Identifying the genetic factors underlying PN could help to better understand its etiology and guide the development of therapies. In thi ... Full text Link to item Cite

Modulation of Neuroimmune and Epithelial Dysregulation in Patients With Moderate to Severe Prurigo Nodularis Treated With Nemolizumab.

Journal Article JAMA Dermatol · September 1, 2023 IMPORTANCE: Prurigo nodularis (PN) is a debilitating skin disease characterized by intense pruritus and hyperkeratotic skin nodules. Nemolizumab, a monoclonal antibody targeting interleukin 31 receptor α, is a promising novel therapy for the treatment of m ... Full text Link to item Cite

Topical GZ21T Inhibits the Growth of Actinic Keratoses in a UVB-Induced Model of Skin Carcinogenesis.

Journal Article JID Innov · July 2023 Actinic keratoses (AKs) are premalignant intraepidermal neoplasms that occur as a result of cumulative sun damage. AKs commonly relapse, and up to 16% undergo malignant transformation into cutaneous squamous cell carcinoma. There is a need for novel therap ... Full text Link to item Cite

Differential Response of Mycosis Fungoides Cells to Vorinostat.

Journal Article Int J Mol Sci · April 29, 2023 Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL) and is characterized by epidermotrophism of malignant CD4+ T-lymphocytes. When MF advances to a recurrent stage, patients require treatment with systemic therapies such as v ... Full text Link to item Cite

Construction of a Secondary Enclosure for UVB Irradiation of Mice.

Journal Article JID Innov · January 2023 UV irradiation is commonly used in murine models of skin cancers. Despite the popularity of using UVB rays to model photocarcinogenesis in animals, there is a lack of standardization in the secondary enclosures used to administer radiation. An appraisal of ... Full text Link to item Cite

Cutaneous Toxicities Associated with Immune Checkpoint Inhibitors: An Observational, Pharmacovigilance Study.

Journal Article J Invest Dermatol · November 2022 Cutaneous immune-related adverse events (cirAEs) are the most prevalent complication to arise from immunotherapy and cause significant morbidity. We aimed to determine the spectrum, timing, clinical features, and outcomes of cirAEs by conducting an observa ... Full text Link to item Cite

Cluster Analysis of Circulating Plasma Biomarkers in Prurigo Nodularis Reveals a Distinct Systemic Inflammatory Signature in African Americans.

Journal Article J Invest Dermatol · May 2022 Patients with prurigo nodularis (PN) suffer from intractable itch and dramatic reduction in QOL. Although there is significant clinical heterogeneity in the presentation of PN, disease endotypes remain unknown. We assayed circulating plasma cytokine concen ... Full text Link to item Cite

GZ17-6.02 Inhibits the Growth of EGFRvIII+ Glioblastoma.

Journal Article Int J Mol Sci · April 10, 2022 Epidermal Growth Factor Receptor (EGFR) is amplified in over 50% of glioblastomas and promotes tumor formation and progression. However, attempts to treat glioblastoma with EGFR tyrosine kinase inhibitors have been unsuccessful thus far. The current standa ... Full text Link to item Cite

Extracellular matrix and dermal nerve growth factor dysregulation in prurigo nodularis compared to atopic dermatitis.

Journal Article Front Med (Lausanne) · 2022 Prurigo nodularis (PN) is a chronic, pruritic, inflammatory skin disease characterized by hyperkeratotic nodules on the trunk and extremities. While there is growing research on the immunological basis of PN, the neuropathic and structural components of PN ... Full text Link to item Cite

Prurigo Nodularis Is Characterized by Systemic and Cutaneous T Helper 22 Immune Polarization.

Journal Article J Invest Dermatol · September 2021 Prurigo nodularis (PN) is an understudied, chronic inflammatory skin disease that disproportionately affects African Americans and presents with intensely pruritic nodules of unknown etiology. To better characterize the immune dysregulation in PN, PBMCs an ... Full text Link to item Cite

Receptors

Chapter · July 29, 2021 Full text Cite

Janus kinase inhibitors for atopic dermatitis: a promising treatment modality.

Journal Article Clin Exp Dermatol · July 2021 Atopic dermatitis (AD) is chronic, pruritic, inflammatory skin disease that affects a significant portion of the population in industrialized nations. For nonresponders to conventional therapies, AD can significantly reduce sleep quality and quality of lif ... Full text Link to item Cite

IL-31 Inhibition as a Therapeutic Approach for the Management of Chronic Pruritic Dermatoses.

Journal Article Drugs · June 2021 Chronic pruritus is a debilitating symptom with limited treatment options. Identifying molecular targets underlying chronic pruritic dermatoses is essential for the development of novel, targeted therapies. IL-31 is an important mediator of itch by integra ... Full text Link to item Cite

Transcriptomic analysis of atopic dermatitis in African Americans is characterized by Th2/Th17-centered cutaneous immune activation.

Journal Article Sci Rep · May 27, 2021 Atopic dermatitis (AD) often presents more severely in African Americans (AAs) and with greater involvement of extensor areas. To investigate immune signatures of AD in AAs with moderate to severe pruritus, lesional and non-lesional punch biopsies were tak ... Full text Link to item Cite

Translational Relevance of Mouse Models of Atopic Dermatitis.

Journal Article J Clin Med · February 6, 2021 The complexity of atopic dermatitis (AD) continues to present a challenge in the appropriate selection of a mouse model because no single murine model completely recapitulates all aspects of human AD. This has been further complicated by recent evidence of ... Full text Link to item Cite

Sleep disturbance in adults with chronic pruritic dermatoses is associated with increased C-reactive protein levels.

Journal Article J Am Acad Dermatol · February 2021 BACKGROUND: Pruritus is a common symptom that can significantly reduce quality of life through sleep disruption. OBJECTIVE: To examine features of disturbed sleep in patients with chronic pruritic dermatoses and test the hypothesis that systemic inflammati ... Full text Link to item Cite

Mouse models for actinic keratoses.

Journal Article J Pharmacol Toxicol Methods · 2021 Actinic keratoses (AKs) represent a premalignant skin condition due to chronic sun damage that dramatically increases in prevalence in the aging population. Currently, animal models of AKs utilize photocarcinogenesis, chemical carcinogens, or targeted gene ... Full text Link to item Cite

Efficacy of osimertinib against EGFRvIII+ glioblastoma.

Journal Article Oncotarget · June 2, 2020 Epidermal Growth Factor Receptor variant III (EGFRvIII) is an active mutant form of EGFR that drives tumor growth in a subset of glioblastoma (GBM). It occurs in over 20% of GBMs, making it a promising receptor for small molecule targeted therapy. We hypot ... Full text Link to item Cite

Association between Prurigo Nodularis and Etiologies of Peripheral Neuropathy: Suggesting a Role for Neural Dysregulation in Pathogenesis.

Journal Article Medicines (Basel) · January 8, 2020 Background: Prurigo nodularis (PN) is an intensely pruritic skin condition of considerable morbidity. However, the pathogenesis of PN and its association with underlying neuropathy is unclear. Objective: We sought to investigate the association between PN ... Full text Link to item Cite

Proteomic and Phosphoproteomic Analysis Reveals that Neurokinin-1 Receptor (NK1R) Blockade with Aprepitant in Human Keratinocytes Activates a Distinct Subdomain of EGFR Signaling: Implications for the Anti-Pruritic Activity of NK1R Antagonists.

Journal Article Medicines (Basel) · December 9, 2019 Background: Epidermal growth factor receptor (EGFR) inhibitors can cause serious cutaneous toxicities, including pruritus and papulopustular acneiform skin eruptions. Increasingly, the neurokinin-1 receptor (NK1R) antagonist aprepitant is being utilized as ... Full text Link to item Cite

Diagnostic Workup and Evaluation of Patients with Prurigo Nodularis.

Journal Article Medicines (Basel) · September 26, 2019 Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized oftentimes by symmetrically distributed, severely pruritic nodules. Currently, the pathophysiology of PN remains to be fully elucidated, but emerging evidence suggests that neuroim ... Full text Link to item Cite

A Rational Approach to Target the Epidermal Growth Factor Receptor in Glioblastoma.

Journal Article Curr Cancer Drug Targets · 2017 Glioblastoma (GBM) is a deadly brain cancer, and all attempts to control it have failed so far. However, the future looks bright, as we now know the molecular landscape of GBM through the work of The Cancer Genome Atlas (TCGA) program. GBMs exhibit signifi ... Full text Link to item Cite

Aprepitant for the Treatment of Chronic Refractory Pruritus.

Journal Article Biomed Res Int · 2017 Chronic pruritus is a difficult condition to treat and is associated with several comorbidities, including insomnia, depression, and decreased quality of life. Treatment for chronic itch includes corticosteroids, antihistamines, and systemic therapies such ... Full text Link to item Cite

Association between Serum IGF-I levels and Postoperative Delirium in Elderly Subjects Undergoing Elective Knee Arthroplasty.

Journal Article Sci Rep · February 5, 2016 Evidence is mixed for an association between serum insulin-like growth factor-I (IGF-I) levels and postoperative delirium (POD). The current study assessed preoperative serum IGF-I levels as a predictor of incident delirium in non-demented elderly elective ... Full text Link to item Cite

Proteomic profiling of patient-derived glioblastoma xenografts identifies a subset with activated EGFR: implications for drug development.

Journal Article J Neurochem · June 2015 The development of drugs to inhibit glioblastoma (GBM) growth requires reliable pre-clinical models. To date, proteomic level validation of widely used patient-derived glioblastoma xenografts (PDGX) has not been performed. In the present study, we characte ... Full text Link to item Cite

Delirium and Obstructive Sleep Apnea: Exploring the Molecular Link

Journal Article Current Anesthesiology Reports · March 1, 2015 Delirium is a common problem among the elderly. The incidence of delirium will increase considerably in the coming decades as the proportion of the population over age 65 increases. Given that an FDA-approved drug to treat delirium is not available, effort ... Full text Cite

Obstructive sleep apnea and delirium: exploring possible mechanisms.

Journal Article Sleep Breath · March 2014 INTRODUCTION: Obstructive sleep apnea (OSA) is a medical disorder strongly associated with multiple comorbidities and postoperative complications. Current evidence suggests that OSA disturbs fundamental biochemical processes, leading to low-grade systemic ... Full text Link to item Cite

Revisiting the prehypertension debate: increasing evidence for treatment yet randomized clinical trials are lacking.

Journal Article Blood Press · December 2013 In 2009, Blood Pressure featured a debate about whether to treat patients with prehypertension (Kiely et al., Blood Press. 2009;18:300-303; McInnes GT, Blood Press. 2009;18:304-307). Our group supported pharmacotherapy for this condition at that time. Sinc ... Full text Link to item Cite

Propofol and the risk of delirium: exploring the anticholinergic properties of propofol.

Journal Article Med Hypotheses · October 2013 Delirium is a common pathologic event in both medical and surgical patients. It is essential to note that patients who develop delirium have worse long term outcomes. The etiology and pathogenesis of delirium are extremely complex and not entirely understo ... Full text Link to item Cite

Delirium after cardiac surgery: have we overlooked obstructive sleep apnea?

Journal Article Med Hypotheses · July 2013 Obstructive sleep apnea is common in patients with cardiovascular disease. It is well known that cardiac surgery is a risk factor for delirium. Researchers have shown that obstructive sleep apnea is an independent risk factor for the occurrence of delirium ... Full text Link to item Cite

Tachykinin/Substance P/Neurokinin-1 Receptors

Chapter · February 15, 2013 Tachykinins are small peptides, found in both vertebrates and invertebrates, which regulate many physiological processes. They are distributed mainly in the central nervous system, but are also important regulators of contractility in vascular smooth muscl ... Full text Cite

In reply.

Journal Article Anesthesiology · December 2012 Full text Link to item Cite

Insulin-like growth factor 1 and delirium.

Journal Article Int Psychogeriatr · November 2012 Full text Link to item Cite

Obstructive sleep apnea and incidence of postoperative delirium after elective knee replacement in the nondemented elderly.

Journal Article Anesthesiology · April 2012 BACKGROUND: Postoperative delirium, a common complication in the elderly, can occur following any type of surgery and is associated with increased morbidity and mortality; it may also be associated with subsequent cognitive problems. Effective therapy for ... Full text Link to item Cite

Prevention of intraoperative awareness.

Journal Article N Engl J Med · November 24, 2011 Full text Link to item Cite

A constitutively active form of neurokinin 1 receptor and neurokinin 1 receptor-mediated apoptosis in glioblastomas.

Journal Article J Neurochem · May 2009 Previous studies have shown that neurokinin 1 receptor (NK1R) occurs naturally in human glioblastomas and its stimulation causes cell proliferation. In the present study we show that stimulation of NK1R in human U373 glioblastoma cells by substance P incre ... Full text Link to item Cite

Treating prehypertension: medically sound and economically viable.

Journal Article Blood Press · 2009 The 7th Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure provided new guide-lines for the definition and management of hypertension. Notably, a new category-"prehypertension"-was created for intermediate s ... Full text Link to item Cite

Limitations of the anticholinergic risk scale.

Journal Article Arch Intern Med · November 24, 2008 Full text Link to item Cite

Selective activation of human atrial Galpha12 and Galpha13 by Galphaq-coupled angiotensin and endothelin receptors.

Journal Article J Cardiovasc Pharmacol · September 2007 Galphaq-coupled receptors such as alpha1-adrenergic, angiotensin, and endothelin receptors, play key roles in cardiac physiology. These receptors have also been shown to couple to G proteins of the G12 family, including Galpha12 and Galpha13. In this repor ... Full text Link to item Cite

Delirium in older persons.

Journal Article N Engl J Med · June 8, 2006 Featured Publication Link to item Cite

Delirium in older persons [11]

Journal Article New England Journal of Medicine · June 8, 2006 Cite

Prevention of atrial fibrillation following cardiac surgery.

Journal Article JAMA · May 17, 2006 Featured Publication Full text Link to item Cite

Signal transduction through substance P receptor in human glioblastoma cells: roles for Src and PKCdelta.

Journal Article Cancer Chemother Pharmacol · December 2005 Featured Publication Substance P receptor (SPR), a G protein-coupled receptor (GPCR), is found in human glioblastomas, and has been implicated in their growth. Consistent with a role for SPR in cell growth, activation of SPR in U373 MG human glioblastoma cells leads to the pho ... Full text Link to item Cite

G alpha(q)-coupled receptors in human atrium function through protein kinase C epsilon and delta.

Journal Article J Mol Cell Cardiol · February 2005 Featured Publication Cardiac G alpha(q)-coupled receptors (such as endothelin, angiotensin, and alpha1-adrenergic receptors) mediate cardiac inotropy and chronotropy, as well as the development of hypertrophy. These receptors signal through protein kinase C (PKC), a family of ... Full text Link to item Cite

Increased expression of Gi-coupled muscarinic acetylcholine receptor and Gi in atrium of elderly diabetic subjects.

Journal Article Diabetes · September 2004 In an ongoing investigation of the effects of age on G protein-coupled receptor signaling in human atrial tissue, we have found that the density of atrial muscarinic acetylcholine receptor (mAChR) increases with age but reaches statistical significance onl ... Full text Link to item Cite

Age increases expression and receptor-mediated activation of G alpha i in human atria.

Journal Article J Cardiovasc Pharmacol · November 2003 Recently, we demonstrated that beta2AR and several other Galphas-coupled receptors in human atria also couple to Galphai, a G protein that inhibits adenylyl cyclase (AC). The present study was undertaken to determine whether age increases expression of Gal ... Full text Link to item Cite

Human substance P receptor lacking the C-terminal domain remains competent to desensitize and internalize.

Journal Article J Neurochem · February 2003 Substance P receptor (SPR) and its naturally occurring splice-variant, lacking the C-terminal tail, are found in brain and spinal cord. Whether C-terminally truncated SPR desensitizes like full-length SPR is controversial. We used a multivaried approach to ... Full text Link to item Cite

Cardiopulmonary bypass decreases G protein-coupled receptor kinase activity and expression in human peripheral blood mononuclear cells.

Journal Article Anesthesiology · February 2003 Featured Publication BACKGROUND: Cardiopulmonary bypass (CPB) has been implicated in the development of organ injury associated with cardiac surgery. At the molecular level, CPB is accompanied by a pronounced proinflammatory response including an increase in plasma interleukin ... Full text Link to item Cite

Age increases cardiac Galpha(i2) expression, resulting in enhanced coupling to G protein-coupled receptors.

Journal Article J Biol Chem · August 23, 2002 Cardiac G protein-coupled receptors that function through stimulatory G protein Galpha(s), such as beta(1)- and beta(2)-adrenergic receptors (beta(1)ARs and beta(2)ARs), play a key role in cardiac contractility. Recent data indicate that several Galpha(s)- ... Full text Link to item Cite

Human substance P receptor undergoes agonist-dependent phosphorylation by G protein-coupled receptor kinase 5 in vitro.

Journal Article FEBS Lett · June 19, 2002 G protein-coupled receptor kinases (GRKs) phosphorylate agonist-occupied G protein-coupled receptors, leading to receptor desensitization. Seven GRKs, designated GRK1 through 7, have been characterized. GRK5 is negatively regulated by protein kinase C. We ... Full text Link to item Cite

Beta(2)-adrenergic and several other G protein-coupled receptors in human atrial membranes activate both G(s) and G(i).

Journal Article Circ Res · October 13, 2000 Cardiac G protein-coupled receptors that couple to Galpha(s) and stimulate cAMP formation (eg, beta-adrenergic, histamine, serotonin, and glucagon receptors) play a key role in cardiac inotropy. Recent studies in rodent cardiac myocytes and transfected cel ... Full text Link to item Cite

β2-Adrenergic and several other g protein-coupled receptors in human atrial membranes activate both G(s) and G(i)

Journal Article Circulation Research · 2000 Cardiac G protein-coupled receptors that couple to Gα(s) and stimulate cAMP formation (eg, β-adrenergic, histamine, serotonin, and glucagon receptors) play a key role in cardiac inotropy. Recent studies in rodent cardiac myocytes and transfected cells have ... Cite

Characterization of differences between rapid agonist-dependent phosphorylation and phorbol ester-mediated phosphorylation of human substance P receptor in intact cells.

Journal Article Mol Pharmacol · May 1999 Featured Publication Substance P receptor (SPR), which plays a key role in pain transmission, is known to undergo rapid agonist-dependent desensitization and internalization. The present study shows that human SPR undergoes agonist-dependent phosphorylation in intact cells. Im ... Link to item Cite

Real-time visualization of the cellular redistribution of G protein-coupled receptor kinase 2 and beta-arrestin 2 during homologous desensitization of the substance P receptor.

Journal Article J Biol Chem · March 12, 1999 The substance P receptor (SPR) is a G protein-coupled receptor (GPCR) that plays a key role in pain regulation. The SPR desensitizes in the continued presence of agonist, presumably via mechanisms that implicate G protein-coupled receptor kinases (GRKs) an ... Full text Link to item Cite

Acute myocardial beta-adrenergic receptor dysfunction after cardiopulmonary bypass in patients with cardiac valve disease. Duke Heart Center Perioperative Desensitization Group.

Journal Article Circulation · November 10, 1998 BACKGROUND: Patients with cardiac valve disease (CVD) frequently have congestive heart failure (CHF) and chronic myocardial beta-adrenergic receptor (beta AR) desensitization. Cardiac surgery requiring cardiopulmonary bypass (CPB) is associated with increa ... Link to item Cite

Acute myocardial β-adrenergic receptor dysfunction after cardiopulmonary bypass in patients with cardiac valve disease

Journal Article Circulation · November 10, 1998 Background - Patients with cardiac valve disease (CVD) frequently have congestive heart failure (CHF) and chronic myocardial β-adrenergic receptor (βAR) desensitization. Cardiac surgery requiring cardiopulmonary bypass (CPB) is associated with increased pl ... Cite

Acute depression of myocardial beta-adrenergic receptor signaling during cardiopulmonary bypass: impairment of the adenylyl cyclase moiety. Duke Heart Center Perioperative Desensitization Group.

Journal Article Anesthesiology · September 1998 BACKGROUND: Previously the authors showed that myocardial beta-adrenergic (betaAR) function is reduced after cardiopulmonary bypass (CPB) in a canine model Whether CPB results in similar effects on betaAR function in adult humans is not known. Therefore th ... Full text Link to item Cite

Human substance P receptor expressed in Chinese hamster ovary cells directly activates G(alpha q/11), G(alpha s), G(alpha o).

Journal Article FEBS Lett · May 29, 1998 Featured Publication Substance P receptor (SPR) stably expressed in Chinese hamster ovary (CHO) cells stimulates at least three second messenger systems including phosphoinositide hydrolysis, cyclic AMP (cAMP) formation, and arachidonic acid release. Whether these second messe ... Full text Link to item Cite

Multiple potential regulatory elements in the 5' flanking region of the human alpha 1a-adrenergic receptor.

Journal Article DNA Seq · March 1998 In spite of their critical importance in myocardial hypertrophy and benign prostatic hyperplasia, nothing is known about mechanisms underlying transcriptional regulation of alpha 1a-adrenergic receptors (alpha 1aARs). Therefore we cloned 6.2 kb of novel se ... Full text Link to item Cite

Characterization of GRK2-catalyzed phosphorylation of the human substance P receptor in Sf9 membranes.

Journal Article Biochemistry · February 3, 1998 Featured Publication G protein-coupled receptor kinases (GRKs) phosphorylate agonist-occupied G protein-coupled receptors (GPCRs), resulting in GPCR desensitization. GRK2 is one of the better studied of the six known GRKs and phosphorylates several GPCRs. In a previous study, ... Full text Link to item Cite

Human substance P receptor expressed in Sf9 cells couples with multiple endogenous G proteins.

Journal Article J Recept Signal Transduct Res · January 1998 To identify the G proteins involved in the function of human substance P receptor (hSPR), the receptor was expressed in Sf9 cells using the baculovirus expression system. Maximal hSPR expression was up to 65 pmol/mg membrane protein. The following data ind ... Full text Link to item Cite

Membrane-bound human substance p receptor undergoes agonist-dependent phosphorylation by g protein receptor kinase 2 (grk2) to a high stoichiometry and activates grk2 in the absence of gβγ

Journal Article FASEB Journal · December 1, 1997 We expressed the human substance P receptor (hSPR) in Sf9 cells at high levels (>50 pmol/mg membrane protein) and examined its ability to serve as GRK2 substrate in intact membranes. The hSPR in Sf9 membranes was phosphorylated by purified GRK2 in agonist- ... Cite

α1,-Adrenoceptor Subtypes in the Human Cardiovascular and Urogenital Systems

Journal Article Advances in Pharmacology · December 1, 1997 Full text Cite

Transcriptional regulation of the human alpha1a-adrenergic receptor gene. Characterization Of the 5'-regulatory and promoter region.

Journal Article J Biol Chem · November 7, 1997 We recently cloned cDNAs encoding three subtypes of human alpha1-adrenergic receptors (alpha1ARs), alpha1a, alpha1b, and alpha1d (Schwinn, D. A., Johnston, G. L., Page, S. O., Mosley, M. J., Wilson, K. H., Worman, N. P., Campbell, S., Fidock, M. D., Furnes ... Full text Link to item Cite

Human G(alpha q): cDNA and tissue distribution.

Journal Article Biochim Biophys Acta · June 11, 1996 G(alpha q), a member of the Gq family of heterotrimeric G proteins, transduces signals from several G protein-coupled receptors that stimulate membrane phosphoinositide hydrolysis. In order to further define the role of G(alpha q) in the function of G prot ... Full text Link to item Cite

Immunoaffinity purification of epitope-tagged human beta 2-adrenergic receptor to homogeneity.

Journal Article Protein Expr Purif · December 1995 To obtain large quantities of pure human beta 2-adrenergic receptor (beta 2-AR) needed for structural studies, an efficient method for beta 2-AR purification was developed using a recombinant receptor with an eight amino acid epitope at its C-terminus. Thi ... Full text Link to item Cite

Cardiac muscarinic potassium channel activity is attenuated by inhibitors of G beta gamma.

Journal Article Circ Res · May 1995 The cardiac muscarinic potassium channel (IK.ACh) is activated by a G protein upon receptor stimulation with acetylcholine. The G protein subunit responsible for activation (G alpha versus G beta gamma) has been disputed. We used G beta gamma inhibitors de ... Full text Link to item Cite

A highly conserved tyrosine residue in G protein-coupled receptors is required for agonist-mediated beta 2-adrenergic receptor sequestration.

Journal Article J Biol Chem · January 28, 1994 An aromatic residue, tyrosine 326 in the prototypical human beta 2-adrenergic receptor, exists in a highly conserved sequence motif in virtually all members of the G protein-coupled receptor family. The potential role of this conserved aromatic amino acid ... Link to item Cite

Partially purified and reconstituted g-protein coupled receptors as substrates of specific receptor kinases

Journal Article Methods · January 1, 1994 Most members of the G-protein-coupled receptor (GPCR) superfamily, which includes several hundred receptors, exhibit agonist-induced desensitization. Studies with rhodopsin and β2-adrenergic receptors indicate that a key biochemical event underlying the pr ... Full text Cite

Functional consequences of A1 adenosine-receptor phosphorylation by the beta-adrenergic receptor kinase.

Journal Article Biochim Biophys Acta · October 7, 1993 Treatment of smooth-muscle cells with R-phenylisopropyladenosine (R-PIA) leads to a loss of A1 adenosine receptor (A1AR)-mediated inhibition of adenylate cyclase, a decrease in receptor number and an increase in receptor phosphorylation. In this study, the ... Full text Link to item Cite

The substance P receptor, which couples to Gq/11, is a substrate of beta-adrenergic receptor kinase 1 and 2.

Journal Article J Biol Chem · May 5, 1993 Featured Publication The agonist-occupied forms of several G-protein-coupled receptors that modulate the activity of adenylycyclase via Gs (e.g. beta 2-adrenergic) or Gi (e.g. alpha 2-adrenergic and cardiac muscarinic) are phosphorylated by beta-adrenergic receptor kinases (be ... Link to item Cite

Beta-arrestin2, a novel member of the arrestin/beta-arrestin gene family.

Journal Article J Biol Chem · September 5, 1992 Homologous or agonist-specific desensitization of beta 2-adrenergic receptors (beta 2AR) is mediated by the beta-adrenergic receptor kinase (beta ARK) which specifically phosphorylates the agonist-occupied form of the receptor. However, the capacity of bet ... Link to item Cite

β-arrestin2, a novel member of the arrestin/β-arrestin gene family

Journal Article Journal of Biological Chemistry · September 5, 1992 Homologous or agonist-specific desensitization of β2-adrenergic receptors (β2AR) is mediated by the β-adrenergic receptor kinase (βARK) which specifically phosphorylates the agonist-occupied form of the receptor. However, the capacity of βARK-phosphorylate ... Cite

Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors.

Journal Article Science · August 28, 1992 The rate and extent of the agonist-dependent phosphorylation of beta 2-adrenergic receptors and rhodopsin by beta-adrenergic receptor kinase (beta ARK) are markedly enhanced on addition of G protein beta gamma subunits. With a model peptide substrate it wa ... Full text Link to item Cite

The ligand binding domain of the epidermal growth factor receptor is not required for receptor dimerization.

Journal Article Biochim Biophys Acta · March 16, 1992 Featured Publication To examine the role of the ligand binding domain of epidermal growth factor receptor in its dimerization, we studied the dimerization of a truncated form of the receptor that resembles v-erbB in that it lacks a ligand binding domain. Receptor dimerization ... Full text Link to item Cite

Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma.

Journal Article Proc Natl Acad Sci U S A · June 1990 We have investigated human gliomas that amplify and rearrange the epidermal growth factor receptor gene, with generation of an in-frame deletion mutation of 802 nucleotides in the external domain. This in-frame deletion mutation generates a local amino aci ... Full text Link to item Cite

Phosphorylation of chick heart muscarinic cholinergic receptors by the beta-adrenergic receptor kinase.

Journal Article Biochemistry · May 30, 1989 Previous studies have demonstrated that muscarinic cholinergic receptors (mAChR) become markedly phosphorylated when intact cardiac cells are stimulated with a muscarinic agonist. This process appears to be related to the process of receptor desensitizatio ... Full text Link to item Cite

The porcine heart M2 muscarinic receptor: agonist-induced phosphorylation and comparison of properties with the chick heart receptor.

Journal Article Mol Pharmacol · May 1989 Featured Publication Recently we showed that the chick heart muscarinic acetylcholine receptor is a phosphoprotein in intact cells and that treatment with agonists results in a striking increase in receptor phosphorylation [J. Biol. Chem. 261:12429-12432 (1986)]. Furthermore, ... Link to item Cite

Characterization of cardiac A1 adenosine receptors by ligand binding and photoaffinity labeling.

Journal Article J Pharmacol Exp Ther · March 1988 [125I]N6-(p-aminobenzyl)adenosine and [125I]N6-(p-azidobenzyl)adenosine, which are potent agonists at A1 (Ri) adenosine receptors, have been used to characterize the adenosine receptor in membranes prepared from newborn chick heart. Scatchard analyses of [ ... Link to item Cite

Correlation of agonist-induced phosphorylation of chick heart muscarinic receptors with receptor desensitization.

Journal Article J Biol Chem · December 5, 1987 Featured Publication We have determined whether the process of agonist-mediated phosphorylation of the muscarinic receptor correlates with the process of muscarinic receptor desensitization in chick cardiac tissue. Exposure of ventricular slices to the agonist carbachol under ... Link to item Cite

N6-phenyladenosines: pronounced effect of phenyl substituents on affinity for A2 adenosine receptors.

Journal Article J Med Chem · May 1987 A number of N6-phenyladenosines with various substitutions on the phenyl ring have been synthesized and tested for their affinities toward brain A1 and A2 adenosine receptors. Compounds with meta substituents, such as (m-hydroxy- and m-iodophenyl)adenosine ... Full text Link to item Cite

N6-phenyladenosines: Pronounced effect of phenyl substituents on affinity for A2 adenosine receptors

Journal Article Journal of Medicinal Chemistry · 1987 A number of N6-phenyladenosines with various substitutions on the phenyl ring have been synthesized and tested for their affinities toward brain A1 and A2 adenosine receptors. Compounds with meta substituents, such as (m-hydroxy-and m-iodophenyl)adenosine, ... Cite

Phosphorylation of the cardiac muscarinic receptor in intact chick heart and its regulation by a muscarinic agonist.

Journal Article J Biol Chem · September 25, 1986 Featured Publication We have tested the possibility that regulation of cardiac muscarinic receptor function may involve receptor phosphorylation. Chick heart muscarinic receptors were purified from relatively small amounts of tissue to near homogeneity using a three-step chrom ... Link to item Cite

Specific photoaffinity labelling of inhibitory adenosine receptors.

Journal Article Biochem Biophys Res Commun · August 30, 1985 N6(L-phenylisopropyl)adenosine (L-PIA) and N6(3-iodo-4-azido benzyl)-adenosine (IAzBA) inhibit the adenylate cyclase activity in synaptic membranes of chick cerebellum via Ri adenosine receptors. [3H]L-PIA and [125I]AzBA bind to these membranes with Kd val ... Full text Link to item Cite

Acetylenics. 2. Synthesis and pharmacology of certain N,N-diakyl-3-phenylpropyn-2-amines. Some analogues with tryptamine-like behavioral effects in mice.

Journal Article J Med Chem · March 1978 A number of N,N-dialkyl-3-phenylpropyn-2-amines 7 have been prepared and tested for their biological action. Certain analogues show tryptamine-like behavior effects in mice. The tryptamine-like activity of these compounds appears to be controlled by their ... Full text Link to item Cite