Concentration‐Response Relationship of α1‐Adrenoceptor‐Stimulated Increase of 86Rb+ Efflux in Rat Heart*

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Abstract
The aim of the present study was to establish a concentration-response relationship for the alpha 1-adrenoceptor mediated increase of 86Rb+ efflux, and to characterize the sensitivity of this response to the selective alpha 1-adrenoceptor antagonist prazosin. Isolated rat hearts were perfused retrogradely at constant flow and at 31 degrees. Timolol (10(-6) mol/l) was used to block beta-adrenoceptors. After a loading period with 86Rb+ 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 alpha 1-adrenoceptor stimulation on 86Rb+ efflux and 42K+ efflux were performed. alpha 1-Adrenoceptor stimulation increased the 86Rb+ efflux with a pD2 = 6.35 +/- 0.20 (mean +/- S.E.M). The maximal response to phenylephrine was 22.5 +/- 2.0% (mean +/- S.E.M.) of the control values. The concentration-response curve was shifted to higher concentration of agonist in the presence of the alpha 1-adrenoceptor antagonist prazosin (3 x 10(10) mol/l). The calculated inhibition constant for prazosin was 6.1 x 10(-11) mol/l. 86Rb+ was found to be a suitable K+ analogue in the study of relative changes in K+ efflux although the basal efflux kinetics were different for the two isotopes. Phenylephrine increased the 86+b+ efflux concentration-dependently. A high sensitivity to prazosin confirmed the involvement of the alpha 1-adrenoceptor population.