The classical competitive antagonism of phentolamine on smooth muscle preparations, investigated by two procedures.
1. In isolated smooth muscle tissues taken from rats, rabbits and guinea-pigs, all at 37.5 degrees C, the equilibrium dissociation constant (K(beta)) of the competitive, reversible alpha-adrenoceptor antagonist phentolamine varied between 4 and 28 nm. 2. The concentration of the antagonist required to inhibit contractions to direct- or indirect-acting alpha-adrenenoceptor agonists by 50% (IC50) also varied between 5 and 30 nm. 3. From one tissue to another, the IC50/K(beta) ratio of the blocker varied from 1 to 2.5, the values being close to those predicted by classical receptor theory based on the law of mass action. 4. At 27.5 degrees C, using phenylephrine as the spasmogen in rat aorta, the IC50/K(beta) ratio for phentolamine was 3.1. 5. A significantly higher IC50 compared with K(beta) for phentolamine indicates that the procedures for estimating affinity constants for a competitive antagonist are not equivalent.
Patil
P N
PN
Division of Pharmacology, College of Pharmacy (LM Parks Hall), The Ohio State University, 500 W. 12th Avenue, Columbus, OH 43210-1291, USA.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001667:Binding, Competitive; D006168:Guinea Pigs; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D010646:Phentolamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D010646:Phentolamine