REGULATION OF G-PROTEINS BY ADENOSINE RECEPTOR AGONIST IN CORONARY-ARTERY

We have previously reported that prolonged exposure of coronary artery to 2-chloroadenosine (CAD) desensitizes the adenosine receptor withou t altering the beta-receptor-mediated response (Am. J. Physiol. 264 (H eart Circ. Physiol. 33): H441-H447, 1993). In the present study, alpha -subunits of guanine nucleotide binding proteins, stimulatory (G(s)) a nd inhibitory (G(i)), were measured using bacterial toxin-catalyzed AD P ribosylation along with a functional response to G(i) protein (throu gh muscarinic receptor activation) in the arteries treated with CAD. I solated coronary arteries were incubated with and without CAD in cultu re 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. S imilarly, the 3-day treatment of the arteries with CAD (10(-8)-10(-4) M) produced a concentration-dependent decrease in cholera toxin-cataly zed ADP ribosylation of 45-kDa protein. Unlike cholera toxin, the alte rations in ADP ribosylation of 41-kDa protein catalyzed by pertussis t oxin was biphasic, an increase at lower concentration of CAD (10(-8)-1 0(-6) M) followed by a decrease at higher concentration of CAD (10(-5) -10(-4) M). The contraction-response curve to methacholine, a muscarin ic receptor agonist, was significantly shifted to the left in the vasc ular rings treated with a low concentration of CAD (10(-6) M) while wi thout an effect at high concentration (10(-4) M) of CAD. The data sugg est that CAD exposure regulates the alpha-subunits of both G(s) and G( i) in coronary artery. The increase in G(i) alpha seems to be the cont ributing factor in elevating the muscarinic receptor-mediated contract ile response in the coronary artery.