AJP - Endocrinology and Metabolism, Vol 268, Issue 4 E693-E704, Copyright © 1995 by American Physiological Society

ARTICLES

Evidence for regulated coupling of A1 adenosine receptors by phosphorylation in Zucker rats

D. A. Berkich, D. R. Luthin, R. L. Woodard, S. J. Vannucci, J. Linden and K. F. LaNoue
Department of Cellular and Molecular Physiology, Hershey Medical Center, Pennsylvania State University 17033, USA.

Studies were designed to find the molecular basis for previous observations that lipolysis is less active and A1 adenosine receptor signaling is more active in adipocytes from obese than from lean Zucker rats. With quantitative immunoblot procedures for detection, Gi alpha 1 and Gs alpha 45 levels were found anomalously low in obese compared with lean membranes (50 and 30%, respectively), but other G alpha subunit levels were normal. However, the sensitivity of the receptor-Gi protein to GTP was about 5- to 10-fold higher in obese compared with lean membranes when assessed from 1) the ability of GTP to inhibit forskolin-stimulated adenylyl cyclase in the presence of an adenosine receptor agonist and 2) the ability of a nonhydrolyzable guanine nucleotide analogue to alter A1 adenosine receptor agonist binding. Alkaline phosphatase treatment of isolated adipocyte membranes from obese but not lean animals decreased guanine nucleotide sensitivity of agonist binding. Surprisingly, solubilized adipocyte A1 adenosine receptors from all animals exhibited the same high sensitivity to guanine nucleotides as that of intact obese membranes, and this high sensitivity could be decreased 20-fold by treatment with alkaline phosphatase. These data suggest that protein phosphorylation may regulate coupling of the A1 adenosine receptor in rat adipocyte membranes.

This article has been cited by other articles:

				G. FRUHBECK, J. GOMEZ-AMBROSI, and J. SALVADOR Leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes FASEB J, February 1, 2001; 15(2): 333 - 340. [Abstract] [Full Text] [PDF]

				G. H. Crist, B. Xu, K. F. Lanoue, and C. H. Lang Tissue-specific effects of in vivo adenosine receptor blockade on glucose uptake in Zucker rats FASEB J, October 1, 1998; 12(13): 1301 - 1308. [Abstract] [Full Text]

				V. Ralevic and G. Burnstock Receptors for Purines and Pyrimidines Pharmacol. Rev., September 1, 1998; 50(3): 413 - 492. [Abstract] [Full Text] [PDF]

				B. Xu, D. A. Berkich, G. H. Crist, and K. F. LaNoue A1 adenosine receptor antagonism improves glucose tolerance in Zucker rats Am J Physiol Endocrinol Metab, February 1, 1998; 274(2): E271 - E279. [Abstract] [Full Text] [PDF]

				H. L. Fox, S. R. Kimball, L. S. Jefferson, and C. J. Lynch Amino acids stimulate phosphorylation of p70S6k and organization of rat adipocytes into multicellular clusters Am J Physiol Cell Physiol, January 1, 1998; 274(1): C206 - C213. [Abstract] [Full Text] [PDF]

				Z. Nie, Y. Mei, and V. Ramkumar Short Term Desensitization of the A1 Adenosine Receptors in DDT1MF-2 Cells Mol. Pharmacol., September 1, 1997; 52(3): 456 - 464. [Abstract] [Full Text]