Activation of a Single Alpha-1-Adrenoceptor Subtype in Rat Aorta Mobilizes Intracellular and Extracellular Pools of Calcium

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Abstract
The calcium channel antagonist, nifedipine (0.1 μM), only slightly inhibited the response to the full α1-adrenoceptor agonist, (–)-norepinephrine, in rat aorta, but nearly completely inhibited the response to the partial αi-adrenoceptor agonist, (–)-dobutamine, indicating that (–)-norepinephrine primarily utilizes intracellular stores of calcium to produce vasoconstriction, whereas (–)-dobutamine relies primarily upon the translocation of extracellular calcium. It has been proposed that the different pools of calcium mobilized by (–)-norepinephrine and (–)-dobutamine in rat aorta result from the activation of two different α1-adrenoceptor subtypes by these agonists. Because the irreversible αi-adrenoceptor antagonist, phenoxybenzamine, has been proposed to inactivate an α1-adrenoceptor subtype coupled specifically to the mobilization of intracellular stores of calcium, this compound should selectively inhibit the response of (–)-norepinephrine, and not the response of (–)-dobutamine, if two distinct α1-adrenoceptor subtypes exist in rat aorta. In the present study, phenoxybenzamine produced concentration-dependent, noncompetitive inhibition of the responses to both agonists in rat aorta, and the pA2’ values for phenoxybenzamine were 8.12 ± 0.23 and 7.74 ± 0.27 against (–)-dobutamine and (–)-norepinephrine, respectively, which are not significantly different from each other (p > 0.05). In addition, the phasic and tonic components of the response to (–)-norepinephrine, which are mediated by the mobilization of intracellular calcium and the translocation of extracellular calcium, respectively, are also inhibited to the same extent by phenoxybenzamine. The results do not support the hypothesis of two α1-adrenoceptor subtypes in rat aorta, one of which being coupled to the translocation of extracellular calcium, and the other to the mobilization of intracellular calcium. Rather, the results support our previous hypothesis that a single α1-adrenoceptor subtype exists in vascular smooth muscle, and this α1-adrenoceptor is coupled to two distinct signal transduction processes, one of which elicits the mobilization of intracellular calcium, and the other opens membrane calcium channels to permit the influx of extracellular calcium.

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