Analysis of effects of adrenaline and collagen on the activity of prostaglandin E1-stimulated human platelet adenylyl cyclase.
A mathematical model relating the activity of adenylyl cyclase (AC) with concentrations of inhibitors, equilibrium dissociation constants, specific activity and efficacies of AC depending on the states of binding sites of the receptors was used for analysis of the data on inhibition of PGE1-stimulated AC of human platelet membranes (Farndale et al. Biochem J 1992; 282; 25-32). The equilibrium dissociation constant, x2 characterizing the affinity of adrenaline for its receptor, was estimated to be 0.14 microM; this constant is a better characteristic of adrenaline's potency than IC50, the concentration corresponding to half-asymptotic inhibition of AC. Collagen does not affect the affinity of adrenaline for its receptor. G protein involved in inhibition of AC activity by collagen is different from Gi2 mediating inhibition by alpha 2-adrenergic agonists. The model applied for the analysis may be thought to be the best means presently to relate dose-response dependencies to what is known or can be hypothesized about the mechanisms underlying inhibition of AC activity.
Juska
A
A
Institute of Biochemistry, Vilnius, Lithuania. Ajuska@ktl.mii.Lt
D000262:Adenylyl Cyclases / Q000097:blood*; D000527:Alprostadil / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D003094:Collagen / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D008962:Models, Theoretical
D003094:Collagen; D000262:Adenylyl Cyclases; D000527:Alprostadil; D004837:Epinephrine