Effects of indoramin in rat vas deferens and aorta: concomitant α₁‐adrenoceptor and neuronal uptake blockade

Abstract

1 The actions of the a 1 -adrenoceptor antagonist indoramin have been examined against the contractions induced by noradrenaline in the rat vas deferens and aorta taking into account a putative neuronal uptake blocking activity 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 values 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 mM) the 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 noradrenaline 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 a 1 -adrenoceptors and neuronal uptake in rat vas deferens resulting in Schild plots with slopes not di erent from unity even in the absence of selective inhibition of neuronal uptake. As a major consequence of this double mechanism of action, the pA 2 values for this antagonist are underestimated when calculated in situations where the neuronal uptake is active, yielding spurious pK B values.

Effect of cyproterone acetate on alpha1-adrenoceptor subtypes in rat vas deferens

“…In addition, the low potency shown by the α 1D -selective antagonist BMY 7378 against the contractions induced by noradrenaline in both organs further indicates that α 1A -adrenoceptors are involved in this functional response. The conclusion that α 1A -adrenoceptors are involved in the contractions of the vas deferens agrees with previous studies from this and other laboratories (8,(16)(17)(18)(19). Interestingly, the α 1A -adrenoceptor is not the only α 1 -subtype expressed in the rat vas deferens since radioligand binding experiments have detected the presence of α 1A -and α 1B -adrenoceptors (20)(21)(22) and mRNA species for α 1A -, α 1B -and α 1D -subtypes have been detected in this organ (23)(24)(25), and Pupo AS and Avellar MCW, unpublished observations).…”

Serotonergic Properties of the Roots of Clerodendron capitatum

“…The results obtained in this study, indicate that the methanolic extract of CC roots does not produce blocking effect since it fails to antagonize the stimulant effect of adrenaline, an adrenergic agonist [21] , on isolated rabbit aortic strips. In addition, the extract did not show any pharmacological activities on frog rectus abdominus muscles, whereby, no contraction, relaxation or blocking properties towards acetylcholine induced contraction of the skeletal muscle were observed.…”

Selective release of ATP from sympathetic nerves of rat vas deferens by the toxin TsTX‐I from Brazilian scorpion Tityus serrulatus

“…Isotonic contractions were recorded by means of isotonic transducers coupled to a recording system (Ugo Basile), under a load of 1.0 g. Surgically denervated vasa deferentia were also used. Denervation was performed as previously described (Kasuya et al ., 1969; Pupo et al ., 1999). Briefly, the rats were anesthetized by ether inhalation, and a 2 cm suprapubic incision was made to expose the deferential artery and vein close to the prostatic end of the vas, where the hypogastric plexus is located.…”