Preponderance of Beta- over Alpha-adrenoceptors in Mediating the Positive Inotropic Effect of Phenylephrine in the Ferret Ventricular Myocardium

[3H]prazosin bound to the membrane fraction derived from the ferret ventricular muscle with high affinity in a saturable manner (Kd = 0.25 nmol/l and Bmax = 27 fmol/mg protein in the right ventricle). [3H]CGP-12177, a beta-adrenoceptor ligand, bound to the membrane fraction with a Kd value of 0.29 nmol/l and a Bmax of 42 fmol/mg protein. In the isolated ferret papillary muscle driven at 1 Hz at 37 degrees C, phenylephrine elicited a concentration-dependent positive inotropic effect. The maximal effect of phenylephrine was comparable to that of isoprenaline. Prazosin (0.3 mumol/l) shifted the concentration-response curve for phenylephrine slightly but significantly to the right, the maximal response being unaffected. In contrast, bupranolol (0.3 mumol/l) shifted the curve for phenylephrine markedly downwards: the maximal response was depressed significantly to 40% and the curve became less steep. In the presence of prazosin and bupranolol the curve was shifted to the right, being essentially parallel to the control curve. These results indicate that in the ferret ventricular myocardium both alpha- and beta-adrenoceptors mediate the positive inotropic effect of phenylephrine. The extent of contribution of the two classes of adrenoceptor is quite different from that in other mammalian species. In the ferret heart, beta-adrenoceptors predominate over alpha-adrenoceptors in mediating the positive inotropic effect of phenylephrine, although the number of beta-adrenoceptors is not especially high when compared with other species.