Determination of agonist affinity for cardiac β-adrenoceptors during reserpine-induced supersensitivity

Abstract

The positive inotropic responses to orciprenaline of paced left atria and papillary muscles and the positive chronotropic responses of spontaneously beating right atria of guinea-pigs were recorded. Tissues from guinea-pigs pretreated with reserpine exhibited supersensitivity to β-adrenoceptor stimulation as demonstrated by the significantly lower EC 50 values to orciprenaline. The antagonism of these responses by Ro 03-7894 was characteristics of irreversible β-adrenoceptor blockade - depression of maximum response and resistant to washout. The dissociation constants (K A) of orciprenaline were determined from the concentration-response curves obtained before and after Ro 03-7894, and no difference was found between tissues from untreated and reserpine-pretreated animals. K A values were also determined from the functional antagonism of the responses by carbachol. The degree of antagonism was less after reserpine pretreatment, but there was no increase in K A value. The reserpine-induced supersensitivity does not therefore appear to be due to an increase in agonist affinity for the cardiac β-adrenoceptor.