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

M Campos,P.L Morais,A.S Pupo

doi:10.1590/s0100-879x2003001100015

M Campos, P.L Morais + Show 1 more

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https://doi.org/10.1590/s0100-879x2003001100015

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Abstract

Gonadal hormones regulate the expression of alpha1-adrenoceptor subtypes in several tissues. The present study was carried out to determine whether or not cyproterone acetate, an anti-androgenic agent, regulates the alpha1-adrenoceptor subtypes that mediate contractions of the rat vas deferens in response to noradrenaline. The actions of subtype selective alpha1-antagonists were investigated in vas deferens from control and cyproterone acetate-treated rats (10 mg/day, sc, for 7 days). Prazosin (pA2 approximately 9.5), phentolamine (pA2 approximately 8.3) and yohimbine (pA2 approximately 6.7) presented competitive antagonism consistent with activation of alpha1-adrenoceptors in vas deferens from both control and treated rats. The pA2 values estimated for WB 4101 ( approximately 9.5), benoxathian ( approximately 9.7), 5-methylurapidil (approximately 8.5), indoramin ( approximately 8.7) and BMY 7378 ( approximately 6.8) indicate that alpha1A-adrenoceptors are involved in the contractions of the vas deferens from control and cyproterone acetate-treated rats. Treatment of the vas deferens from control rats with the alpha1B/alpha1D-adrenoceptor alkylating agent chloroethylclonidine had no effect on noradrenaline contractions, supporting the involvement of the alpha1A-subtype. However, this agent partially inhibited the contractions of vas deferens from cyproterone acetate-treated rats, suggesting involvement of multiple receptor subtypes. To further investigate this, the actions of WB 4101 and chloroethylclonidine were reevaluated in the vas deferens from rats treated with cyproterone acetate for 14 days. In these organs WB 4101 presented complex antagonism characterized by a Schild plot with a slope different from unity (0.65 0.05). After treatment with chloroethylclonidine, the complex antagonism presented by WB 4101 was converted into classical competitive antagonism, consistent with participation of alpha1A-adrenoceptors as well as alpha1B-adrenoceptors. These results suggest that cyproterone acetate induces plasticity in the alpha1-adrenoceptor subtypes involved in the contractions of the vas deferens.

Highlights

Three different α1-adrenoceptor subtypes, α1A, α1B- and α1D-adrenoceptors, have been cloned [1]
In vas deferens from control rats and from rats treated with cyproterone acetate for 7 days, the antagonists WB 4101 and benoxathian (α1A/α1D-selective), indoramin and 5-methylurapidil (α1A-selective), and BMY 7378 (α1D-selective) inhibited noradrenaline contractions showing competitive antagonisms (Figure 3 and Table 2)
We investigated the effects of treatment with the anti-androgen cyproterone acetate on α1-adrenoceptor subtypes involved in the contractions of the rat vas deferens in response to noradrenaline using subtype-selective competitive antagonists

Summary

Introduction

Three different α1-adrenoceptor subtypes, α1A-, α1B- and α1D-adrenoceptors, have been cloned [1]. Additional α1-adrenoceptor heterogeneity has been suggested by functional studies in which prazosin showed low potency in inhibiting contractions of certain vascular tissues in response to adrenergic agonists [2]. Prazosin shows low potency for inhibition of [3H]-inositol phosphate formation in cell lines expressing each of the human α1A-adrenoceptor splice variants, suggesting that these additional subtypes may represent low affinity state(s) of the α1Aadrenoceptors and not a different protein encoded by a different gene [3,4]. Some studies have shown that gonadal hormones differentially regulate the expression of α1-adrenoceptor subtypes in several tissues [6,7,8,9,10,11,12]. Previous data from our laboratory have shown that castration changes the α1-adrenoceptor subtypes involved in the contractions of the rat vas deferens in response to noradrenaline [8] and that testosterone replacement treatment of castrated rats prevents this plasticity [12]

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