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Title: Adenosine analogues decrease myocardial. beta. -adrenergic receptor affinity for isoproterenol

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6802387

Adenosine and its analogues have been shown to attenuate catecholamine-induced activation of adenylate cyclase in rat myocardial membranes via adenosine R/sub i/ (inhibitory) receptors. The effects of adenosine analogues on binding characteristics of ..beta..-adrenergic receptors (BAR) in rat heart ventricular membranes were examined in the present study. Neither phenylisopropyladenosine (PIA, 1..mu..M) nor 2-chloroadenosine (CADO, 10..mu..M) significantly influenced /sup 125/I-cyanopinodolol (ICYP) binding to membranes as assessed by BAR affinity (Kd, 20 pM) or concentration (B/sub max/, 35 fmol/mg protein). However, in isoproterenol (ISO)-ICYP competition experiments, PIA, an R/sub i/ agonist, significantly shifted the ISO competition curve to the right 3.6 fold. The IC/sub 50/s of control and PIA treated membranes were 5.04 x 10/sup -8/M, and 1.81 X 10/sup -7/M respectively. The slope of the control curve (-0.58) was also increased in the PIA treated membranes (-0.94). CADO, a less specific adenosine R/sub i/ receptor agonist, shifted the curve to the right only 2 fold and increased the slope from -0.5 to -0.75. 2',5'-dideoxyadenosine, an adenosine P-site agonist, had no significant effect on ISO binding. These data suggest that adenosine R/sub i/ agonists may attenuate catecholamine-induced activation of adenylate cyclase by decreasing the affinity of BAR for agonists.

Research Organization:
Univ. of Massachusetts Medical School, Worcester
OSTI ID:
6802387
Report Number(s):
CONF-8604222-; TRN: 87-008604
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
Country of Publication:
United States
Language:
English