Receptor-mediated mutual-effect amplification elicited by phenylephrine and serotonin in isolated rabbit aorta.
Phenylephrine (PE) and 5-hydroxytryptamine (5-HT) were utilized to study the effects of simultaneous coactivation of the alpha-1 and 5-HT2 receptors, respectively, on the contractile response of isolated rabbit aortic rings. A mutual-effect amplification of the PE-induced contractile response was observed with concentration-response curves (CRC) elicited by mixtures of PE and 5-HT, using a novel drug concentration paradigm. The theoretical CRC constructed using the Poch and Holzman method of equiactive agonist substitution demonstrated that the observed mutual-effect amplification was more than the result of simple additivity. Thus, the Leff model of mutual-effect amplification was utilized to predict the location of observed CRCs to mixtures of PE and 5-HT. Efficacy (tau) and slope factor estimates were determined using the Black and Leff operational model of pharmacological agonism and these values were used to predict the location of CRCs elicited by mixtures of PE and 5-HT. We demonstrated that the Leff model was insufficient to explain the observed degree of mutual-effect amplification.
Christ
G J
GJ
Department of Urology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York.
Goldfarb
J
J
Maayani
S
S
D000818:Animals; D001011:Aorta / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D066298:In Vitro Techniques; D008297:Male; D008954:Models, Biological; D010656:Phenylephrine / Q000494:pharmacology*; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D015398:Signal Transduction; D014661:Vasoconstriction / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D010656:Phenylephrine; D012701:Serotonin