RESUMEN
The contractions of the rat vas deferens in response to noradrenaline are mediated through alpha(1A)-adrenoceptors. We observed participation of alpha(1B)-adrenoceptors in these contractions after castration. We now investigated the time course of this plasticity and the effects of testosterone by determining the actions of competitive antagonists on noradrenaline-induced contractions after 7, 14, 21 and 30 days of castration. BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride) antagonised noradrenaline-induced contractions in control and castrated rats with low pA(2) values (approximately = 6.8). In control vas deferens, WB 4101 (2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride) had a slope in the Schild plot no different from 1.0, while slopes lower than 1.0 (approximately 0.6) were observed for vas deferens from castrated rats. Chloroethylclonidine was ineffective in the control vas while it inhibited noradrenaline-induced contractions in vasa from castrated rats and converted the complex antagonism by WB 4101 into simple competitive antagonism. Treatment of castrated rats with testosterone prevented the effects of castration. The results suggest that alpha(1B)-adrenoceptors are detectable in vas deferens from at least the 7th through the 30th day after castration and that testosterone prevents this plasticity.
Asunto(s)
Castración , Clonidina/análogos & derivados , Receptores Adrenérgicos alfa 1/efectos de los fármacos , Testosterona/administración & dosificación , Testosterona/uso terapéutico , Conducto Deferente/efectos de los fármacos , Animales , Clonidina/administración & dosificación , Clonidina/farmacocinética , Dioxanos/administración & dosificación , Dioxanos/farmacocinética , Relación Dosis-Respuesta a Droga , Masculino , Contracción Muscular , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Norepinefrina/administración & dosificación , Norepinefrina/antagonistas & inhibidores , Norepinefrina/farmacocinética , Fentolamina/administración & dosificación , Fentolamina/farmacocinética , Piperazinas/administración & dosificación , Piperazinas/farmacocinética , Prazosina/administración & dosificación , Prazosina/farmacocinética , Ratas , Ratas Wistar , Receptores Adrenérgicos alfa 1/fisiología , Factores de Tiempo , Yohimbina/administración & dosificación , Yohimbina/farmacocinéticaRESUMEN
The expression of alpha 1-adrenoceptor subtypes in several tissues is regulated by gonadal hormones. In this study, we investigated whether castration regulates the alpha 1-adrenoceptor subtypes mediating the contractions of the aorta from male rats to noradrenaline. Noradrenaline induced similar concentration-dependent contractions in the aorta from control and castrated rats. Treatment of the aorta from both control and castrated rats with the alpha 1B/alpha 1D-adrenoceptor alkylating agent chloroethylclonidine resulted in approximately 1600-fold rightward shift in the concentration-response curves to noradrenaline. The pA2 values found for WB 4101, benoxathian (alpha 1A-selective) and BMY 7378 (alpha 1D-selective) indicate that alpha 1D-adrenoceptors are involved in the contractions of the aorta from control and castrated rats to noradrenaline. However, there was a 15-fold difference between the pKB estimated through the lowest effective concentrations of the alpha 1A-adrenoceptor selective antagonist 5-methyl-urapidil in the aorta from control and castrated rats. The pKB estimated in aorta from control rats is consistent with the interaction with alpha 1D-adrenoceptors (7.58 +/- 0.06), while that calculated in organs from control rats is consistent with alpha 1A-adrenoceptors (8.76 +/- 0.09). These results suggest that castration induces plasticity in the alpha 1-adrenoceptor subtypes involved in the contractions of the aorta to noradrenaline.