Effects of castration and of testosterone replacement on alpha(1)-adrenoceptor subtypes in the rat vas deferens.
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.
Campos
Marcelo
M
Departmento de Farmacologia, Instituto de Biociências, UNESP, Botucatu, SP 18618-000, Brazil.
Morais
Paola de Lucena
Pde L
Pupo
André S
AS
D000818:Animals; D002369:Castration; D003000:Clonidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004146:Dioxanes / Q000008:administration & dosage / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D010646:Phentolamine / Q000008:administration & dosage / Q000493:pharmacokinetics; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics; D011224:Prazosin / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000502:physiology; D013739:Testosterone / Q000008:administration & dosage* / Q000627:therapeutic use*; D013997:Time Factors; D014649:Vas Deferens / Q000187:drug effects*; D015016:Yohimbine / Q000008:administration & dosage / Q000493:pharmacokinetics
C547718:Adra1b protein, rat; D004146:Dioxanes; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D015016:Yohimbine; C051731:chlorethylclonidine; D013739:Testosterone; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; C053428:BMY 7378; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine