Contraction of Rat Cauda Epididymis Smooth Muscle to α₁-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 α₁-adrenoceptors (α₁-ARs) plays a key role during the seminal emission phase of ejaculation and α₁-AR antagonism has been suggested as a nonhormonal and reversible male contraceptive target. Since the α₁-AR subtype mediating contraction of rat CE is not known, this study investigates the expression and role of α₁-AR subtypes on the proximal and distal rat CE duct contraction to norepinephrine in vitro. Alpha_1a, 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 [³H]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 (pK_B ≈ 9.50) and 5-methylurapidil (pK_B ≈ 9.0) and with low affinity by BMY 7378 (pK_B ≈ 7.0) and the α_1B-selective L-765,314 (pA₂ < 7.0), suggesting contractions are mediated by α_1A-ARs. The clinically used α_1A/D-ARs antagonist tamsulosin potently (pA₂ ≈ 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.