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

Publication ,  Journal Article
Gainetdinov, RR; Bohn, LM; Walker, JK; Laporte, SA; Macrae, AD; Caron, MG; Lefkowitz, RJ; Premont, RT
Published in: 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 the GRK5 gene (GRK5-KO) were generated. GRK5-KO mice exhibited mild spontaneous hypothermia as well as pronounced behavioral supersensitivity upon challenge with the nonselective muscarinic agonist oxotremorine. Classical cholinergic responses such as hypothermia, hypoactivity, tremor, and salivation were enhanced in GRK5-KO animals. The antinociceptive effect of oxotremorine was also potentiated and prolonged. Muscarinic receptors in brains from GRK5-KO mice resisted oxotremorine-induced desensitization, as assessed by oxotremorine-stimulated [5S]GTPgammaS binding. These data demonstrate that elimination of GRK5 results in cholinergic supersensitivity and impaired muscarinic receptor desensitization and suggest that a deficit of GPCR desensitization may be an underlying cause of behavioral supersensitivity.

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Published In

Neuron

DOI

ISSN

0896-6273

Publication Date

December 1999

Volume

24

Issue

4

Start / End Page

1029 / 1036

Location

United States

Related Subject Headings

  • Recombination, Genetic
  • Receptors, Muscarinic
  • Protein Serine-Threonine Kinases
  • Pain Measurement
  • Oxotremorine
  • Neurology & Neurosurgery
  • Muscarinic Agonists
  • Motor Activity
  • Mice, Knockout
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gainetdinov, R. R., Bohn, L. M., Walker, J. K., Laporte, S. A., Macrae, A. D., Caron, M. G., … Premont, R. T. (1999). Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice. Neuron, 24(4), 1029–1036. https://doi.org/10.1016/s0896-6273(00)81048-x
Gainetdinov, R. R., L. M. Bohn, J. K. Walker, S. A. Laporte, A. D. Macrae, M. G. Caron, R. J. Lefkowitz, and R. T. Premont. “Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice.Neuron 24, no. 4 (December 1999): 1029–36. https://doi.org/10.1016/s0896-6273(00)81048-x.
Gainetdinov RR, Bohn LM, Walker JK, Laporte SA, Macrae AD, Caron MG, et al. Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice. Neuron. 1999 Dec;24(4):1029–36.
Gainetdinov, R. R., et al. “Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice.Neuron, vol. 24, no. 4, Dec. 1999, pp. 1029–36. Pubmed, doi:10.1016/s0896-6273(00)81048-x.
Gainetdinov RR, Bohn LM, Walker JK, Laporte SA, Macrae AD, Caron MG, Lefkowitz RJ, Premont RT. Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice. Neuron. 1999 Dec;24(4):1029–1036.
Journal cover image

Published In

Neuron

DOI

ISSN

0896-6273

Publication Date

December 1999

Volume

24

Issue

4

Start / End Page

1029 / 1036

Location

United States

Related Subject Headings

  • Recombination, Genetic
  • Receptors, Muscarinic
  • Protein Serine-Threonine Kinases
  • Pain Measurement
  • Oxotremorine
  • Neurology & Neurosurgery
  • Muscarinic Agonists
  • Motor Activity
  • Mice, Knockout
  • Mice