Contraction of Rat Cauda Epididymis Smooth Muscle to alpha(1)-Adrenoceptor Activation Is Mediated by alpha(1A)-Adrenoceptors

Abstract

The cauda epididymis (CE), the site of sperm storage until the ejaculation, is densely innervated by the sympathetic nervous system. Contraction of CE smooth muscle via alpha(1)-adrenoceptors (alpha(1)-ARs) plays a key role during the seminal emission phase of ejaculation and alpha(1)-AR antagonism has been suggested as a nonhormonal and reversible male contraceptive target. Since the alpha(1)-AR subtype mediating contraction of rat CE is not known, this study investigates the expression and role of alpha(1)-AR subtypes on the proximal and distal rat CE duct contraction to norepinephrine in vitro. Alpha(1a), alpha(1b), and alpha(1d) transcripts were detected by real-time quantitative polymerase chain reaction in proximal and distal CE segments and alpha(1a) and alpha(1d) were shown to predominate over alpha(1b). The inhibition of [H-3]prazosin specific binding to intact CE segments from proximal and distal CE by RS 100329 and 5-methylurapidil (alpha(1A)-selective) and BMY 7378 (alpha(1D)-selective) showed that alpha(1A)- and alpha(1D)-ARs are expressed at similar densities. Norepinephrine-induced contractions of CE were competitively antagonized with high affinity by RS 100329 (pK(B) approximate to 9.50) and 5-methylurapidil (pK(B) approximate to 9.0) and with low affinity by BMY 7378 (pK(B) approximate to 7.0) and the alpha(1B)-selective L-765,314 (pA(2) < 7.0), suggesting contractions are mediated by alpha(1A)-ARs. The clinically used alpha(1A/D)-ARs antagonist tamsulosin potently (pA(2) approximate to 10.0) inhibited the norepinephrine-induced CE contractions. Altogether, our results show that alpha(1A)- and alpha(1D)-ARs are expressed in the CE duct and alpha(1A)-AR is the main subtype mediating contraction to norepinephrine. Our results highlight the importance of alpha(1A)-AR in the peripheral control of ejaculation and strengthen the alpha(1)A(-)AR as a target for a nonhormonal approach to male contraception.