Postsynaptic α‐adrenoceptor reserve and the shift of the concentration‐response curves to the right, as caused by the irreversible α‐adrenoceptor antagonist phenoxybenzamine

Open Access
Publisher Website
Google Scholar
Abstract
1 The effect of different concentrations of phenoxybenzamine (0.1, 0.3, 1, 3, 10 and 30 nmol l−1) on the concentration-response curves to phenylephrine (a selective α1-adrenoceptor agonist) and noradrenaline (a mixed α1- and α2-adrenoceptor agonist) was compared in two kinds of vascular tissue: dog saphenous vein (has both postsynaptic α1- and α2-adrenoceptors) and dog mesenteric and renal arteries—where only postsynaptic α1-adrenoceptors have been shown to exist. 2 In the saphenous vein, where both α1- and α2-adrenoceptors coexist, at only one concentration of phenoxybenzamine, 3 nmol l−1, the concentration-response curve of noradrenaline was shifted to the right without a reduction of the maximum; and this shift was small (by 0.4 log units). 3 In tissues where only α1-adrenoceptors exist postsynaptically (mesenteric and renal arteries) phenoxybenzamine never caused any shift of the noradrenaline concentration-response curves to the right without depressing the maximum effect. 4 In none of the tissues did phenoxybenzamine at any concentration shift the concentration-response curve of phenylephrine to the right without depressing its maximum. 5 All these results indicate that in the dog saphenous vein there is a ‘false’ α-adrenoceptor reserve for noradrenaline, since two kinds of receptors participate in the response to this amine. 6 The calculation of the occupancy-response relationship for the renal artery showed that 24% of the maximal response occurs when only 2% of α1-adrenoceptors are activated and 50% of maximum at 9% occupation. However, for 95% of the maximal response an 83% occupancy is required. Similar values were calculated for the mesenteric artery. 7 Thus, the surplus α1-adrenoceptors which is very large for a half-maximal response becomes smaller and smaller as the magnitude of the response increases and probably disappears at the 100% response level. 8 If we retain the original definition of ‘spare receptors’–receptors in ‘excess’ of those required to produce a maximal response, we conclude, that there is no receptor reserve in the dog mesenteric and renal arteries.