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

Publication ,  Journal Article
Walker, JK; Peppel, K; Lefkowitz, RJ; Caron, MG; Fisher, JT
Published in: 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 important mechanism involved in the dampening of GPCR signaling. To determine whether this mechanism might play a role in airway smooth muscle physiology, we examined the airway pressure time index and heart rate (HR) responses to intravenous administration of the cholinergic agonist methacholine (MCh) in genetically altered mice lacking one copy of GRK2 (GRK2 +/-), homozygous GRK3 knockout (GRK3 -/-), and wild-type littermates. (GRK2 -/- mice die in utero.) GRK3 -/- mice demonstrated a significant enhancement in the airway response to 100 and 250 microgram/kg doses of MCh compared with wild-type and GRK2 +/- mice. GRK3 -/- mice also displayed an enhanced sensitivity of the airway smooth muscle response to MCh. In addition, GRK3 -/- mice displayed an altered HR recovery from MCh-induced bradycardia. Although direct stimulation of cardiac muscarinic receptors measured as vagal stimulation-induced bradycardia was similar in GRK3 -/- and wild-type mice, the baroreflex increase in HR associated with sodium nitroprusside-induced hypotension was significantly greater in GRK3 -/- than wild-type mice. Therefore, these data demonstrate that in the mouse, GRK3 may be involved in modulating the cholinergic response of airway smooth muscle and in regulating the chronotropic component of the baroreceptor reflex.

Duke Scholars

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

April 1999

Volume

276

Issue

4

Start / End Page

R1214 / R1221

Location

United States

Related Subject Headings

  • Vagus Nerve
  • Receptor Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Propranolol
  • Nitroprusside
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Methacholine Chloride
  • Injections, Intravenous
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Walker, J. K., Peppel, K., Lefkowitz, R. J., Caron, M. G., & Fisher, J. T. (1999). Altered airway and cardiac responses in mice lacking G protein-coupled receptor kinase 3. Am J Physiol, 276(4), R1214–R1221. https://doi.org/10.1152/ajpregu.1999.276.4.R1214
Walker, J. K., K. Peppel, R. J. Lefkowitz, M. G. Caron, and J. T. Fisher. “Altered airway and cardiac responses in mice lacking G protein-coupled receptor kinase 3.Am J Physiol 276, no. 4 (April 1999): R1214–21. https://doi.org/10.1152/ajpregu.1999.276.4.R1214.
Walker JK, Peppel K, Lefkowitz RJ, Caron MG, Fisher JT. Altered airway and cardiac responses in mice lacking G protein-coupled receptor kinase 3. Am J Physiol. 1999 Apr;276(4):R1214–21.
Walker, J. K., et al. “Altered airway and cardiac responses in mice lacking G protein-coupled receptor kinase 3.Am J Physiol, vol. 276, no. 4, Apr. 1999, pp. R1214–21. Pubmed, doi:10.1152/ajpregu.1999.276.4.R1214.
Walker JK, Peppel K, Lefkowitz RJ, Caron MG, Fisher JT. Altered airway and cardiac responses in mice lacking G protein-coupled receptor kinase 3. Am J Physiol. 1999 Apr;276(4):R1214–R1221.

Published In

Am J Physiol

DOI

ISSN

0002-9513

Publication Date

April 1999

Volume

276

Issue

4

Start / End Page

R1214 / R1221

Location

United States

Related Subject Headings

  • Vagus Nerve
  • Receptor Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Propranolol
  • Nitroprusside
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Methacholine Chloride
  • Injections, Intravenous