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 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)
Hussain
T
T
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858.
Mustafa
S J
SJ
D015762:2-Chloroadenosine / Q000494:pharmacology*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001158:Arteries; D002772:Cholera Toxin / Q000494:pharmacology; D003331:Coronary Vessels / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D016210:Methacholine Chloride / Q000494:pharmacology; D009994:Osmolar Concentration; D037342:Pertussis Toxin; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013552:Swine; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D018047:Receptors, Purinergic P1; D010566:Virulence Factors, Bordetella; D016210:Methacholine Chloride; D015762:2-Chloroadenosine; D000246:Adenosine Diphosphate Ribose; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins