Effects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockade

1 The actions of the alpha(1)-adrenoceptor antagonist indoramin have been e xamined against the contractions induced by noradrenaline in the rat vas de ferens and aorta taking into account a putative neuronal uptake blocking ac tivity of this antagonist which could. result in self-cancelling actions. 2 Indoramin behaved as a simple competitive antagonist of the contractions induced by noradrenaline in the vas deferens and aorta yielding pA(2) value s of 7.38 +/- 0.05 (slope = 0.98 +/- 0.03) and 6.78 +/- 0.14 (slope = 1.08 +/- 0.06), respectively. 3 When the experiments were repeated in the presence of cocaine (6 mu M) th e potency (pA(2)) of indoramin in antagonizing the contractions of the vas deferens to noradrenaline was increased to 8.72 +/- 0.07 (slope = 1.10 +/- 0.05) while its potency remained unchanged in the aorta (pA(2) = 6.69 +/- 0 .12; slope = 1.04 +/- 0.05). 4 In denervated vas deferens, indoramin antagonized the contractions to nor adrenaline with a potency similar to that found in the presence of cocaine (8.79 +/- 0.07; slope = 1.09 +/- 0.06). 5 It is suggested that indoramin blocks alpha(1)-adrenoceptors and neuronal uptake in rat vas deferens resulting in Schild plots with slopes not diffe rent from unity even in the absence of selective inhibition of neuronal upt ake. As a major consequence of this double mechanism of action, the pA(2) v alues for this antagonist are underestimated when calculated in situations where the neuronal uptake is active, yielding spurious pK(B) values.