Julia K.L. Walker

Journal Article J Clin Invest · September 15, 2023 Asthma is a chronic inflammatory disease associated with episodic airway narrowing. Inhaled β2-adrenergic receptor (β2AR) agonists (β2-agonists) promote - with limited efficacy - bronchodilation in asthma. All β2-agonists are canonical orthosteric ligands ... Full text Link to item Cite

Evaluating Associations between Average Pain Intensity and Genetic Variation in People with Sickle Cell Disease: An Exploratory Study.

Journal Article Pain Manag Nurs · February 2023 BACKGROUND: Pain is one of the most common and deleterious symptoms experienced by individuals with sickle cell disease (SCD). There is a paucity of studies identifying potential genetic mechanisms of pain in this population. AIM: Examine associations betw ... Full text Link to item Cite

Vertical sleeve gastrectomy associates with airway hyperresponsiveness in a murine model of allergic airway disease and obesity.

Journal Article Front Endocrinol (Lausanne) · 2023 INTRODUCTION: Asthma is a chronic airway inflammatory disease marked by airway inflammation, remodeling and hyperresponsiveness to allergens. Allergic asthma is normally well controlled through the use of beta-2-adrenergic agonists and inhaled corticostero ... Full text Open Access Link to item Cite

Exogenous leptin enhances markers of airway fibrosis in a mouse model of chronic allergic airways disease.

Journal Article Respir Res · May 24, 2022 BACKGROUND: Asthma patients with comorbid obesity exhibit increased disease severity, in part, due to airway remodeling, which is also observed in mouse models of asthma and obesity. A mediator of remodeling that is increased in obesity is leptin. We hypot ... Full text Open Access Link to item Cite

Severe Persistent Pain and Inflammatory Biomarkers in Sickle Cell Disease: An Exploratory Study.

Journal Article Biol Res Nurs · January 2022 BACKGROUND: Severe pain is among the most common and deleterious symptoms experienced by individuals with sickle cell disease (SCD), of whom more than 50% report chronic pain. Despite this, the understanding of the biological contributors to persistent sev ... Full text Link to item Cite

A deep learning approach to student registered nurse anesthetist (SRNA) education.

Journal Article International journal of nursing education scholarship · June 2021 ObjectivesThis manuscript describes the application of deep learning to physiology education of Student Registered Nurse Anesthetists (SRNA) and the benefits thereof. A strong foundation in physiology and the ability to apply this knowledge to cha ... Full text Cite

Therapeutic Potential of Targeting ß-Arrestin.

Journal Article Frontiers in pharmacology · January 2019 ß-arrestins are multifunctional proteins that modulate heptahelical 7 transmembrane receptors, also known as G protein-coupled receptors (GPCRs), a superfamily of receptors that regulate most physiological processes. ß-arrestin modulation of GPCR function ... Full text Cite

Methods to Investigate the Roles for β-Arrestin-2 in Allergic Inflammatory Airway Disease.

Journal Article Methods in molecular biology (Clifton, N.J.) · January 2019 Spatial and temporal control of gene expression using cre/loxP technology is a major methodological advance for biomedical research. The ability to alter gene expression after an in vivo disease model has been established and allows researchers the opportu ... Full text Cite

β-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T-Helper Type 2 Cells.

Journal Article American journal of respiratory cell and molecular biology · June 2018 Allergic asthma is a complex inflammatory disease that leads to significant healthcare costs and reduction in quality of life. Although many cell types are implicated in the pathogenesis of asthma, CD4+ T-helper cell type 2 (Th2) cells are centr ... Full text Cite

Commentary: Central-acting therapeutics alleviate respiratory weakness caused by heart failure-induced ventilatory overdrive.

Journal Article Front Physiol · 2018 Full text Link to item Cite

β-Arrestin2 mediates progression of murine primary myelofibrosis.

Journal Article JCI Insight · December 21, 2017 Primary myelofibrosis is a myeloproliferative neoplasm associated with significant morbidity and mortality, for which effective therapies are lacking. β-Arrestins are multifunctional adaptor proteins involved in developmental signaling pathways. One isofor ... Full text Link to item Cite

Targeted HAS2 Expression Lessens Airway Responsiveness in Chronic Murine Allergic Airway Disease.

Journal Article Am J Respir Cell Mol Biol · December 2017 Hyaluronan (HA), a major component of the extracellular matrix, is secreted by airway structural cells. Airway fibroblasts in allergic asthma secrete elevated levels of HA in association with increased HA synthase 2 (HAS2) expression. Thus, we hypothesized ... Full text Open Access Link to item Cite

Phosphodiesterase 4 Inhibitors Attenuate the Asthma Phenotype Produced by β2-Adrenoceptor Agonists in Phenylethanolamine N-Methyltransferase-Knockout Mice.

Journal Article American journal of respiratory cell and molecular biology · August 2016 Mice lacking the endogenous β2-adrenoceptor (β2AR) agonist epinephrine (phenylethanolamine N-methyltransferase [PNMT]-knockout mice) are resistant to developing an "asthma-like" phenotype in an ovalbumin sensitization and challenge (Ova S/C) model, and chr ... Full text Cite

Specificity of arrestin subtypes in regulating airway smooth muscle G protein-coupled receptor signaling and function.

Journal Article FASEB journal : official publication of the Federation of American Societies for Experimental Biology · October 2015 Arrestins have been shown to regulate numerous G protein-coupled receptors (GPCRs) in studies employing receptor/arrestin overexpression in artificial cell systems. Which arrestin isoforms regulate which GPCRs in primary cell types is poorly understood. We ... Full text Cite

Genetic Deletion of β-Arrestin-2 and the Mitigation of Established Airway Hyperresponsiveness in a Murine Asthma Model.

Journal Article American journal of respiratory cell and molecular biology · September 2015 β-Arrestin-2 (βarr2) is a ubiquitously expressed cytosolic protein that terminates G protein-coupled receptor signaling and transduces G protein-independent signaling. We previously showed that mice lacking βarr2 do not develop an asthma phenotype when sen ... Full text Cite

Quantification of beta adrenergic receptor subtypes in beta-arrestin knockout mouse airways.

Journal Article PloS one · January 2015 In allergic asthma Beta 2 adrenergic receptors (β2ARs) are important mediators of bronchorelaxation and, paradoxically, asthma development. This contradiction is likely due to the activation of dual signaling pathways that are downstream of G proteins or β ... Full text Cite

Editorial overview: Respiratory: GPCR signaling and the lung.

Journal Article Current opinion in pharmacology · June 2014 Full text Cite

Role for β-arrestin in mediating paradoxical β2AR and PAR2 signaling in asthma.

Journal Article Current opinion in pharmacology · June 2014 G protein-coupled receptors (GPCRs) utilize (at least) two signal transduction pathways to elicit cellular responses including the classic G protein-dependent, and the more recently discovered β-arrestin-dependent, signaling pathways. In human and murine m ... Full text Cite

GPCRs and arrestins in airways: implications for asthma.

Book · January 2014 The obstructive lung disease asthma is treated by drugs that target, either directly or indirectly, G protein-coupled receptors (GPCRs). GPCRs coupled to Gq are the primary mediators of airway smooth muscle (ASM) contraction and increased airway resistance ... Full text Cite

Reply: Adverse effects of long-acting beta-agonists on airway hyperresponsiveness.

Journal Article American journal of respiratory cell and molecular biology · September 2013 Full text Cite

β2-Adrenoceptor agonists are required for development of the asthma phenotype in a murine model.

Journal Article American journal of respiratory cell and molecular biology · February 2013 β(2)-Adrenoceptor (β2AR) agonists are the most effective class of bronchodilators and a mainstay of asthma management. The first potent β2AR agonist discovered and widely used in reversing the airway constriction associated with asthma exacerbation was the ... Full text Cite

Assessment of murine lung mechanics outcome measures: Alignment with those made in asthmatics

Journal Article Frontiers in Physiology · 2013 Although asthma is characterized as an inflammatory disease, recent reports highlight the importance of pulmonary physiology outcome measures to the clinical assessment of asthma control and risk of asthma exacerbation. Murine models of allergic inflammato ... Full text Cite

β-Arrestin-2 mediates the proinflammatory effects of proteinase-activated receptor-2 in the airway.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · October 2012 Featured Publication Proteinase-Activated rreceptor-2 (PAR(2)), a G-protein-coupled Receptor, activated by serine proteinases, is reported to have both protective and proinflammatory effects in the airway. Given these opposing actions, both inhibitors and activators of PAR(2) ... Full text Cite

Chronic treatment in vivo with β-adrenoceptor agonists induces dysfunction of airway β(2) -adrenoceptors and exacerbates lung inflammation in mice.

Journal Article Br J Pharmacol · April 2012 Featured Publication BACKGROUND AND PURPOSE: Inhalation of a β-adrenoceptor agonist (β-agonist) is first-line asthma therapy, used for both prophylaxis against, and acute relief of, bronchoconstriction. However, repeated clinical use of β-agonists leads to impaired bronchoprot ... Full text Link to item Cite

Assessment of murine lung mechanics outcome measures: alignment with those made in asthmatics.

Journal Article Frontiers in physiology · January 2012 Although asthma is characterized as an inflammatory disease, recent reports highlight the importance of pulmonary physiology outcome measures to the clinical assessment of asthma control and risk of asthma exacerbation. Murine models of allergic inflammato ... Full text Cite

New perspectives regarding β(2) -adrenoceptor ligands in the treatment of asthma.

Journal Article British journal of pharmacology · May 2011 Featured Publication In the last two decades several significant changes have been proposed in the receptor theory that describes how ligands can interact with G protein-coupled receptors (GPCRs). Here we briefly summarize the evolution of receptor theory and detail recent pro ... Full text Cite

beta-Adrenoceptor inverse agonists in asthma.

Journal Article Current opinion in pharmacology · June 2010 Featured Publication Beta(2)-adrenoceptor (beta(2)-AR) agonists are very effective bronchodilators and play a major role in every stage of asthma management. However, their chronic, regular use is associated with detrimental effects including an increase in asthma-related deat ... Full text Cite

In A Model Of Innate Immunity The Interaction Between Inducible Nitric Oxide Synthase And Surfactant Protein-A Regulates Airway Responsiveness

Journal Article A108. ALVEOLAR STRESS, INFLAMMATION AND IMMUNITY: SURFACTANT, COLLECTINS, AND BEYOND · May 2010 Full text Cite

Both Hematopoietic- and Non-hematopoietic-derived {beta}-arrestin-2 Regulates Murine Allergic Airway Disease.

Journal Article American journal of respiratory cell and molecular biology · October 2009 Featured Publication Allergic asthma, a major cause of morbidity and leading cause of hospitalizations, is an inflammatory disease orchestrated by T helper cells and characterized by lung migration of eosinophils, important asthma effector cells. Lung migration of inflammatory ... Full text Cite

Beta-arrestins specifically constrain beta2-adrenergic receptor signaling and function in airway smooth muscle.

Journal Article FASEB journal : official publication of the Federation of American Societies for Experimental Biology · July 2008 Featured Publication Chronic use of inhaled beta-agonists by asthmatics is associated with a loss of bronchoprotective effect and deterioration of asthma control. Beta-agonist-promoted desensitization of airway smooth muscle beta-2-adrenergic receptors, mediated by G protein-c ... Full text Cite

Regulation of M2-type pyruvate kinase mediated by the high-affinity IgE receptors is required for mast cell degranulation.

Journal Article Br J Pharmacol · July 2008 BACKGROUND AND PURPOSE: M2-type pyruvate kinase (M2PK) was found to interact directly with the 'ITAM' region of the gamma chain of the high-affinity IgE receptor (FcvarepsilonRI). Our hypothesis was that mast cell degranulation might require the Fcvarepsil ... Full text Link to item Cite

3He MRI in mouse models of asthma.

Journal Article Magn Reson Med · November 2007 In the study of asthma, a vital role is played by mouse models, because knockout or transgenic methods can be used to alter disease pathways and identify therapeutic targets that affect lung function. Assessment of lung function in rodents by available met ... Full text Link to item Cite

A murine model of hyperdopaminergic state displays altered respiratory control.

Journal Article FASEB J · May 2007 The dopamine transporter (DAT) protein plays an important role in the termination of dopamine signaling. We addressed the hypothesis that loss of DAT function would result in a distinctive cardiorespiratory phenotype due to the significant role of dopamine ... Full text Link to item Cite

Leukocyte-derived IL-10 reduces subepithelial fibrosis associated with chronically inhaled endotoxin.

Journal Article Am J Respir Cell Mol Biol · December 2006 Endotoxin (LPS), a Gram-negative cell wall component, has potent proinflammatory properties. Acute LPS exposure causes airway inflammation; chronic exposure causes airway hyperreactivity and remodeling. IL-10 is an important antiinflammatory cytokine, whic ... Full text Link to item Cite

Multistrain genetic comparisons reveal CCR5 as a receptor involved in airway hyperresponsiveness.

Journal Article American journal of respiratory cell and molecular biology · June 2006 Asthma is a ubiquitous disease with a broad range of clinical phenotypes. To better understand the complex genetic and environmental interactions underlying asthma, we compared the gene-gene interactions of four genetically distinct mouse strains that demo ... Cite

Morphine side effects in beta-arrestin 2 knockout mice.

Journal Article The Journal of pharmacology and experimental therapeutics · September 2005 Morphine is a potent analgesic, yet, like most opioid narcotics, it exerts unwanted side effects such as constipation and respiratory suppression, thereby limiting its clinical utility. Pharmacological approaches taken to preserve the analgesic properties, ... Cite

Toll-like receptor 4 antagonist (E5564) prevents the chronic airway response to inhaled lipopolysaccharide.

Journal Article American journal of physiology. Lung cellular and molecular physiology · August 2005 Although chronic inhalation of endotoxin or lipopolysaccharide (LPS) causes all of the classic features of asthma, including airway hyperreactivity, airway inflammation, and airway remodeling, the mechanisms involved in this process are not clearly underst ... Cite

The role of Toll-like receptor 4 in environmental airway injury in mice.

Journal Article American journal of respiratory and critical care medicine · July 2004 Inhalation of toxins commonly found in air pollution contributes to the development and progression of asthma and environmental airway injury. In this study, we investigated the requirement of toll-like receptor 4 (TLR4) in mice for pulmonary responses to ... Cite

beta-arrestin-2 regulation of lung eosinophilia in a mouse model of Th2-type airway inflammation

Conference FASEB JOURNAL · March 23, 2004 Link to item Cite

G protein-coupled receptor kinase 5 regulates airway responses induced by muscarinic receptor activation.

Journal Article Am J Physiol Lung Cell Mol Physiol · February 2004 G protein-coupled receptors (GPCRs) transduce extracellular signals into intracellular events. The waning responsiveness of GPCRs in the face of persistent agonist stimulation, or desensitization, is a necessary event that ensures physiological homeostasis ... Full text Link to item Cite

Beta-arrestin-2 regulates the development of allergic asthma.

Journal Article J Clin Invest · August 2003 Featured Publication Asthma is a chronic inflammatory disorder of the airways that is coordinated by Th2 cells in both human asthmatics and animal models of allergic asthma. Migration of Th2 cells to the lung is key to their inflammatory function and is regulated in large part ... Full text Open Access Link to item Cite

Allergen-induced airway disease is mouse strain dependent.

Journal Article American journal of physiology. Lung cellular and molecular physiology · July 2003 We investigated the development of airway hyperreactivity (AHR) and inflammation in the lungs of nine genetically diverse inbred strains of mice [129/SvIm, A/J, BALB/cJ, BTBR+(T)/tf/tf, CAST/Ei, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ] after sensitization an ... Full text Cite

[beta]-arrestin-2 regulates the development of allergic asthma in mice

Conference FASEB JOURNAL · March 17, 2003 Link to item Cite

Vasoactive intestinal polypeptide type-1 receptor regulation. Desensitization, phosphorylation, and sequestration.

Journal Article The Journal of biological chemistry · July 2002 The vasoactive intestinal polypeptide type-1 (VPAC(1)) receptor is a class II G protein-coupled receptor, distinct from the adrenergic receptor superfamily. The mechanisms involved in the regulation of the VPAC(1) receptor are largely unknown. We examined ... Cite

Mice lacking the dopamine transporter display altered regulation of distal colonic motility.

Journal Article Am J Physiol Gastrointest Liver Physiol · August 2000 The mechanisms by which dopamine (DA) influences gastrointestinal (GI) tract motility are incompletely understood and complicated by tissue- and species-specific differences in dopaminergic function. To improve the understanding of DA action on GI motility ... Full text Link to item Cite

Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity.

Journal Article Proc Natl Acad Sci U S A · February 1, 2000 Recently, we identified a GTPase-activating protein for the ADP ribosylation factor family of small GTP-binding proteins that we call GIT1. This protein initially was identified as an interacting partner for the G protein-coupled receptor kinases, and its ... Full text Open Access Link to item Cite

Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice.

Journal Article Neuron · December 1999 G protein-coupled receptor kinase 5 (GRK5) is a member of a family of enzymes that phosphorylate activated G protein-coupled receptors (GPCR). To address the physiological importance of GRK5-mediated regulation of GPCRs, mice bearing targeted deletion of t ... Full text Link to item Cite

Properties of secretin receptor internalization differ from those of the beta(2)-adrenergic receptor.

Journal Article J Biol Chem · October 29, 1999 The endocytic pathway of the secretin receptor, a class II GPCR, is unknown. Some class I G protein-coupled receptors (GPCRs), such as the beta(2)-adrenergic receptor (beta(2)-AR), internalize in clathrin-coated vesicles and this process is mediated by G p ... Full text Link to item Cite

Altered airway and cardiac responses in mice lacking G protein-coupled receptor kinase 3.

Journal Article Am J Physiol · April 1999 Contraction and relaxation of airway smooth muscles is mediated, in part, by G protein-coupled receptors (GPCRs) and dysfunction of these receptors has been implicated in asthma. Phosphorylation of GPCRs, by G protein-coupled receptor kinase (GRK), is an i ... Full text Link to item Cite

Respiratory effects of pressor and depressor agents in conscious rats.

Journal Article Canadian journal of physiology and pharmacology · July 1998 We hypothesized that the respiratory baroreflex in conscious rats is either more transient, or has a higher pressure threshold than in other species. To characterize the effect of arterial pressure changes on respiration in conscious rats, ventilation (V) ... Full text Cite

Ventilatory and metabolic effects of hypercapnia in conscious rats: AVP V1 receptor block.

Journal Article Canadian journal of physiology and pharmacology · April 1998 In conscious dogs, arginine vasopressin (AVP) inhibits an angiotensin II drive to ventilation during air breathing and during acute hypercapnia. To determine whether AVP inhibits respiration in rats, as in dogs, respiration and metabolism were measured in ... Full text Cite

A role for receptor kinases in the regulation of class II G protein-coupled receptors. Phosphorylation and desensitization of the secretin receptor.

Journal Article J Biol Chem · March 20, 1998 The secretin receptor is a member of a structurally distinct class of G protein-coupled receptors designated as Class II. The molecular mechanisms of secretin receptor signal termination are unknown. Using transiently transfected HEK 293 cells expressing t ... Full text Link to item Cite

Altered cardiac chronotropic responses in βARK 2 knockout mice

Journal Article FASEB Journal · 1998 G protein-coupled receptor kinases (GRKs) desensitize agonist-activated G protein-coupled receptors (GPCRs) thus attenuating their responses. In cell culture experiments, GRK 3 (βARK 2) phosphorylates and desensitizes multiple GPCRs, including muscarinic a ... Cite

Breath timing, volume and drive to breathe in conscious rats: comparative aspects.

Journal Article Respiration physiology · March 1997 In conscious animals, respiratory frequency (f) and tidal volume (VT) vary breath to breath. Examining the average value of variables associated with specific bins of another variable, such as breath f, provides a unique tool to examine respiratory behavio ... Full text Cite

Baroreceptor inhibition of respiration in conscious rats infused with phenylephrine (PE) or angiotensin II (ANG II)

Journal Article FASEB Journal · December 1, 1996 The study was designed to determine 1) if ANG II acts centrally to stimulate ventilation, thus countering baroreflex inhibition of ventilation and, 2) to test the comparative thresholds for cardiac and respiratory baroreceptor reflexes between PE and ANG I ... Cite

Ventilatory effects of angiotensin and vasopressin in conscious rats.

Journal Article Canadian journal of physiology and pharmacology · November 1996 Angiotensin II (ANG II) stimulates ventilation (V), when ventilatory baroreceptor reflexes are taken into account, and arginine vasopressin (AVP) causes baroreflex inhibition of V in conscious and anesthetized dogs. To study mechanisms of hormonal modulati ... Full text Cite

Respiration during acute hypoxia: angiotensin- and vasopressin-receptor blocks.

Journal Article Journal of applied physiology (Bethesda, Md. : 1985) · March 1996 In normoxic conscious dogs, increased angiotensin II (ANG II), or activation (disinhibition) of the renin-angiotensin system by vasopressin (AVP) V1-receptor block, increases ventilation and decreases arterial PCO2. Both hormones can be increased during hy ... Full text Cite

During acute hypercapnia vasopressin inhibits an angiotensin drive to ventilation in conscious dogs.

Journal Article Journal of applied physiology (Bethesda, Md. : 1985) · September 1995 Intravenous infusion of arginine vasopressin (AVP) depresses the slope of the ventilatory response to CO2 during acute hypercapnia. We therefore tested the hypothesis that AVP V1-receptor blockade would increase the slope of the ventilatory response to CO2 ... Full text Cite

Angiotensin mediates stimulation of ventilation after vasopressin V1 receptor blockade.

Journal Article Journal of applied physiology (Bethesda, Md. : 1985) · June 1994 We tested the hypothesis that respiration would be stimulated after vasopressin (AVP) V1 receptor blockade because of disinhibition and activation of the renin-angiotensin system. Intravenous infusion of angiotensin II (ANG II) stimulates respiration, pres ... Full text Cite

Renin-angiotensin system stimulates respiration during acute hypotension but not during hypercapnia.

Journal Article Journal of applied physiology (Bethesda, Md. : 1985) · March 1993 We reported that intravenous infusion of angiotensin II (ANG II) stimulated ventilation (VE) in conscious dogs. Other studies in our laboratory have demonstrated that increases in respiration occurred in association with activation of the renin-angiotensin ... Full text Cite