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