CALCIUM INFLUX DEPENDENT AND CALCIUM INFLUX INDEPENDENT ALPHA-1-ADRENOCEPTOR MEDIATED PROCESSES OF VASOCONSTRICTION INVIVO DO NOT OPERATE VIA DIFFERENT ALPHA-1-ADRENOCEPTOR SUBTYPES

In pithed rats, the selective alpha 1-adrenoceptor agonists St 587 and cirazoline show preponderant calcium influx-dependent and -independent vasoconstriction, respectively. By using these agonists, selective (competitive) antagonists for either process of vasoconstriction were sought. For this purpose, antagonism was analyzed for eight structurally different antagonists (prazosin, BE 2254, AR-C239, R 28935, corynanthine, phentolamine, sulpiride, and chlorpromazine) opposing the pressor responses evoked by cirazoline and St 587. Where pA2 values (-log dose antagonist evoking a twofold shift for the agonist dose-response curve) could be calculated, no significantly different pA2 values against either agonist resulted. However, with respect to the slopes of the Schild plots, deviations from unity were found for prazosin, R 28935, AR-C239, sulpiride, and chlorpromazine, but not uniformly against both agonists. Following treatment with phenoxybenzamine (PB) (30 micrograms/kg) and nifedipine (1 mg/kg), which produced calcium influx-sensitive and -insensitive vasoconstriction to cirazoline, respectively, Schild plots were constructed for BE 2254, prazosin, and chlorpromazine. Using cirazoline as an agonist, unity slopes were now obtained for prazosin and chlorpromazine. The Schild plots of BE 2254 versus cirazoline after PB or nifedipine administration, however, exhibited a slope deviating from unity. For prazosin and chlorpromazine, identical pA2 values still resulted against both processes of vasoconstriction to cirazoline. The results are compatible with the view that alpha 1-adrenoceptors mediating calcium influx-dependent and -independent vasoconstriction in vivo are not distinctly different entities, but are separate recognition sites of the same receptor.