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

Conference · Tue Mar 04 23:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6802387

Romano, F D; Fenton, R A; Dobson, Jr, J G

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-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:4; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADENOSINE
AFFINITY
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CELL MEMBRANES
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HEART
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
MUSCLES
MYOCARDIUM
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RIBOSIDES
RODENTS
SYMPATHOMIMETICS
TRACER TECHNIQUES
VERTEBRATES