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Am J Physiol Heart Circ Physiol 266: H1273-H1279, 1994;
0363-6135/94 $5.00
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AJP - Heart and Circulatory Physiology, Vol 266, Issue 4 1273-H1279, Copyright © 1994 by American Physiological Society

ARTICLES

Regulation of G proteins by adenosine receptor agonist in coronary artery

T. Hussain and S. J. Mustafa
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858.

We have previously reported that prolonged exposure of coronary artery to 2-chloroadenosine (CAD) desensitizes the adenosine receptor without altering the beta-receptor-mediated response (Am. J. Physiol. 264 (Heart Circ. Physiol. 33): H441-H447, 1993). In the present study, alpha-subunits of guanine nucleotide binding proteins, stimulatory (Gs) and inhibitory (Gi), were measured using bacterial toxin-catalyzed ADP ribosylation along with a functional response to Gi protein (through muscarinic receptor activation) in the arteries treated with CAD. Isolated coronary arteries were incubated with and without CAD in culture media. CAD treatment (10(-4) M) resulted in a time-dependent (1, 3, and 7 days) attenuation in the cholera- and pertussis toxin-catalyzed ADP ribosylation of 45- and 41-kDa membrane proteins, respectively. Similarly, the 3-day treatment of the arteries with CAD (10(-8)-10(-4) M) produced a concentration-dependent decrease in cholera toxin-catalyzed ADP ribosylation of 45-kDa protein. Unlike cholera toxin, the alterations in ADP ribosylation of 41-kDa protein catalyzed by pertussis toxin was biphasic, an increase at lower concentration of CAD (10(-8)-10(-6) M) followed by a decrease at higher concentration of CAD (10(-5)-10(-4) M). The contraction-response curve to methacholine, a muscarinic receptor agonist, was significantly shifted to the left in the vascular rings treated with a low concentration of CAD (10(-6) M) while without an effect at high concentration (10(-4) M) of CAD. The data suggest that CAD exposure regulates the alpha-subunits of both Gs and Gi in coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)


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