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

Publication ,  Journal Article
Kwatra, MM; Leung, E; Maan, AC; McMahon, KK; Ptasienski, J; Green, RD; Hosey, MM
Published in: J Biol Chem
December 5, 1987

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 conditions previously shown to lead to large increases in muscarinic receptor phosphorylation (Kwatra, M. M., and Hosey, M. M. (1986) J. Biol. Chem. 261, 12429-12432) resulted in decreased affinity of the muscarinic receptor for agonists. The agonist oxotremorine mimicked and the antagonist atropine prevented the effects of carbachol on receptor phosphorylation and agonist affinity. The time courses and concentration dependences for agonists to induce phosphorylation of the muscarinic receptor and decreases in agonist affinity were similar. Treatment of chick atria with acetylcholine under conditions which led to receptor phosphorylation resulted in decreased sensitivity of these preparations to the negative inotropic effect of carbachol. Taken together, the results support the concept that phosphorylation of cardiac muscarinic receptors may be related to the process of receptor desensitization. The mechanism by which agonists induce receptor phosphorylation was also investigated. The phosphorylated amino acids formed in response to agonists were serine and threonine. The protein kinase C activator phorbol myristate acetate had no effect on receptor phosphorylation or agonist affinity, nor did it prevent the effects of carbachol on either of these parameters. Receptor phosphorylation also was unaffected by the calmodulin antagonists W-7 and W-13, by elevation of cyclic nucleotides, and by agonists which activate other cardiac receptor systems. The results suggest that the phosphorylation of cardiac muscarinic receptors requires agonist occupancy of the receptor and/or may involve the participation of a selective protein kinase.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

December 5, 1987

Volume

262

Issue

34

Start / End Page

16314 / 16321

Location

United States

Related Subject Headings

  • Receptors, Muscarinic
  • Quinuclidinyl Benzilate
  • Phosphorylation
  • Oxotremorine
  • Myocardium
  • Magnesium
  • Heart
  • Guanylyl Imidodiphosphate
  • Dose-Response Relationship, Drug
  • Chickens
 

Citation

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Kwatra, M. M., Leung, E., Maan, A. C., McMahon, K. K., Ptasienski, J., Green, R. D., & Hosey, M. M. (1987). Correlation of agonist-induced phosphorylation of chick heart muscarinic receptors with receptor desensitization. J Biol Chem, 262(34), 16314–16321.
Kwatra, M. M., E. Leung, A. C. Maan, K. K. McMahon, J. Ptasienski, R. D. Green, and M. M. Hosey. “Correlation of agonist-induced phosphorylation of chick heart muscarinic receptors with receptor desensitization.J Biol Chem 262, no. 34 (December 5, 1987): 16314–21.
Kwatra MM, Leung E, Maan AC, McMahon KK, Ptasienski J, Green RD, et al. Correlation of agonist-induced phosphorylation of chick heart muscarinic receptors with receptor desensitization. J Biol Chem. 1987 Dec 5;262(34):16314–21.
Kwatra, M. M., et al. “Correlation of agonist-induced phosphorylation of chick heart muscarinic receptors with receptor desensitization.J Biol Chem, vol. 262, no. 34, Dec. 1987, pp. 16314–21.
Kwatra MM, Leung E, Maan AC, McMahon KK, Ptasienski J, Green RD, Hosey MM. Correlation of agonist-induced phosphorylation of chick heart muscarinic receptors with receptor desensitization. J Biol Chem. 1987 Dec 5;262(34):16314–16321.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

December 5, 1987

Volume

262

Issue

34

Start / End Page

16314 / 16321

Location

United States

Related Subject Headings

  • Receptors, Muscarinic
  • Quinuclidinyl Benzilate
  • Phosphorylation
  • Oxotremorine
  • Myocardium
  • Magnesium
  • Heart
  • Guanylyl Imidodiphosphate
  • Dose-Response Relationship, Drug
  • Chickens