The effects of uptake1 on alpha-adrenoceptor antagonist potency in dog saphenous vein

Abstract

1 The effects of alpha-adrenoceptor antagonists on contractile responses to noradrenaline and methoxamine were examined in isolated saphenous vein strips of the dog. 2 Phentolamine, labetalol and thymoxamine antagonized responses to methoxamine to a greater extent than responses to noradrenaline. 3 Cocaine (3.0 x 10(-5) mol/l) increased the potency of noradrenaline by about eight fold, but had little or no effect on the potency of methoxamine. 4 In the presence of cocaine (3.0 x 10(-5) mol/l) the potency of the antagonists against noradrenaline was increased such that the pA2 values were then similar to those obtained against methoxamine. 5 It is concluded that the lower potency of phentolamine, labetalol and thymoxamine as antagonists of noradrenaline than of methoxamine is due to the presence of an avid saturable uptake1 process in the saphenous vein.