PT - JOURNAL ARTICLE AU - Enio S. A. Pacini AU - Anthony C. S. Castilho AU - Flavia Hebeler-Barbosa AU - André S. Pupo AU - Luiz R. A. Kiguti TI - Contraction of Rat Cauda Epididymis Smooth Muscle to <em>α</em><sub>1</sub>-Adrenoceptor Activation Is Mediated by <em>α</em><sub>1A</sub>-Adrenoceptors AID - 10.1124/jpet.117.246710 DP - 2018 Jul 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 21--28 VI - 366 IP - 1 4099 - http://jpet.aspetjournals.org/content/366/1/21.short 4100 - http://jpet.aspetjournals.org/content/366/1/21.full SO - J Pharmacol Exp Ther2018 Jul 01; 366 AB - 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. Alpha1a, α1b, and α1d transcripts were detected by real-time quantitative polymerase chain reaction in proximal and distal CE segments and α1a and α1d were shown to predominate over α1b. The inhibition of [3H]prazosin specific binding to intact CE segments from proximal and distal CE by RS 100329 and 5-methylurapidil (α1A-selective) and BMY 7378 (α1D-selective) showed that α1A- and α1D-ARs are expressed at similar densities. Norepinephrine-induced contractions of CE were competitively antagonized with high affinity by RS 100329 (pKB ≈ 9.50) and 5-methylurapidil (pKB ≈ 9.0) and with low affinity by BMY 7378 (pKB ≈ 7.0) and the α1B-selective L-765,314 (pA2 &lt; 7.0), suggesting contractions are mediated by α1A-ARs. The clinically used α1A/D-ARs antagonist tamsulosin potently (pA2 ≈ 10.0) inhibited the norepinephrine-induced CE contractions. Altogether, our results show that α1A- and α1D-ARs are expressed in the CE duct and α1A-AR is the main subtype mediating contraction to norepinephrine. Our results highlight the importance of α1A-AR in the peripheral control of ejaculation and strengthen the α1A-AR as a target for a nonhormonal approach to male contraception.