CONCENTRATION-RESPONSE RELATIONSHIP OF ALPHA(1)-ADRENOCEPTOR-STIMULATED INCREASE OF RB-86(-HEART() EFFLUX IN RAT)

The aim of the present study was to establish a concentration-response relationship for the alpha(1)-adrenoceptor mediated increase of Rb-86 (+) efflux, and to characterize the sensitivity of this response to th e selective alpha(2)-adrenoceptor antagonist prazosin. Isolated rat he arts were perfused retrogradely at constant flow and at 31 degrees. Ti molol (10(-6)mol/l) was used to block beta-adrenoceptors. After a load ing period with Rb-86(+) and 55 min. washout, the hearts were exposed to phenylephrine in a concentration range from 3 x 10(-8)mol/l to 10(- 4)mol/l. Control experiments comparing the effects of al-adrenoceptor stimulation on Rb-86(+) efflux and K-42(+) efflux were performed. alph a(1)-Adrenoceptor stimulation increased the Rb-86(+) efflux with a pD( 2) = 6.35 +/- 0.20 (mean +/- S.E.M.). The maximal response to phenylep hrine was 22.5 +/- 2.0% (mean +/- S.E.M.) of the control values. The c oncentration-response curve was shifted to higher concentration of ago nist in the presence of the alpha(1)-adrenoceptor antagonist prazosin (3 x 10(-10) mol/l). The calculated inhibition constant for prazosin w as 6.1 x 10(-11) mol/l. Rb-86(+) was found to be a suitable K+ analogu e in the study of relative changes in K+ efflux although the basal eff lux kinetics were different for the two isotopes. Conclusion: Phenylep hrine increased the Rb-86(+) efflux concentration-dependently. A high sensitivity to prazosin confirmed the involvement of the alpha(1)-adre noceptor population.