Contraction of Rat Cauda Epididymis Smooth Muscle to α 1 -Adrenoceptor Activation Is Mediated by α 1A -Adrenoceptors.

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 α 1 -adrenoceptors ( α 1 -ARs) plays a key role during the seminal emission phase of ejaculation and α 1 -AR antagonism has been suggested as a nonhormonal and reversible male contraceptive target. Since the α 1 -AR subtype mediating contraction of rat CE is not known, this study investigates the expression and role of α 1 -AR subtypes on the proximal and distal rat CE duct contraction to norepinephrine in vitro. Alpha1a , α 1b , and α 1d transcripts were detected by real-time quantitative polymerase chain reaction in proximal and distal CE segments and α 1a and α 1d were shown to predominate over α 1b The inhibition of [3 H]prazosin specific binding to intact CE segments from proximal and distal CE by RS 100329 and 5-methylurapidil ( α 1A -selective) and BMY 7378 ( α 1D -selective) showed that α 1A - and α 1D -ARs are expressed at similar densities. Norepinephrine-induced contractions of CE were competitively antagonized with high affinity by RS 100329 (p K B ≈ 9.50) and 5-methylurapidil (p K B ≈ 9.0) and with low affinity by BMY 7378 (p K B ≈ 7.0) and the α 1B -selective L-765,314 (p A 2 < 7.0), suggesting contractions are mediated by α 1A -ARs. The clinically used α 1A/D -ARs antagonist tamsulosin potently (p A 2 ≈ 10.0) inhibited the norepinephrine-induced CE contractions. Altogether, our results show that α 1A - and α 1D -ARs are expressed in the CE duct and α 1A -AR is the main subtype mediating contraction to norepinephrine. Our results highlight the importance of α 1A -AR in the peripheral control of ejaculation and strengthen the α 1A -AR as a target for a nonhormonal approach to male contraception.