Competitive vs. noncompetitive blockade of epinephrine-sensitive GTPase activity in human platelets.
The manner of inhibition of the epinephrine-stimulated GTPase activity by phentolamine and yohimbine was studied in human platelet membranes. (-)-Epinephrine(1-microM)-stimulated GTPase activity was inhibited concentration-dependently by phentolamine and yohimbine with IC50 values of 150 nM and 25 nM, respectively. Addition of increasing concentrations of phentolamine shifted the concentration-response curve to (-)-epinephrine to the right in a parallel manner. Schild plot analysis gave a KB value of 13 nM and a slope factor of 0.99. Yohimbine inhibited the activity, on the contrary, in a noncompetitive fashion. This inhibition by yohimbine was reversible after thorough washing of the membranes.
Odagaki
Y
Y
Department of Psychiatry and Neurology, Hokkaido University School of Medicine, Sapporo, Japan.
Koyama
T
T
Yamashita
I
I
D001667:Binding, Competitive; D001792:Blood Platelets / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors* / Q000097:blood*; D006801:Humans; D007700:Kinetics; D010646:Phentolamine / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology*
D015016:Yohimbine; D020558:GTP Phosphohydrolases; D004837:Epinephrine; D010646:Phentolamine