Premium
Postsynaptic α‐adrenoceptor reserve and the shift of the concentration‐response curves to the right, as caused by the irreversible α‐adrenoceptor antagonist phenoxybenzamine
Author(s) -
Guimarães Serafini,
Paiva Maria Q.
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb11350.x
Subject(s) - phenoxybenzamine , phenylephrine , postsynaptic potential , medicine , mesenteric arteries , endocrinology , agonist , chemistry , adrenergic receptor , prazosin , receptor , antagonist , artery , blood pressure
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 α 1 ‐adrenoceptor agonist) and noradrenaline (a mixed α 1 ‐ and α 2 ‐adrenoceptor agonist) was compared in two kinds of vascular tissue: dog saphenous vein (has both postsynaptic α 1 ‐ and α 2 ‐adrenoceptors) and dog mesenteric and renal arteries—where only postsynaptic α 1 ‐adrenoceptors have been shown to exist. 2 In the saphenous vein, where both α 1 ‐ and α 2 ‐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 α 1 ‐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 α 1 ‐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 α 1 ‐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.