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 α1-adrenoceptors (α1-ARs) plays a key role during the seminal emission phase of ejaculation and α1-ARs antagonism has been suggested as a non-hormonal and reversible male contraceptive target. As the α1-ARs subtype mediating contraction of rat CE is not known this study investigates the expression and role of α1-ARs subtypes on the proximal and distal rat CE duct contraction to norepinephrine in vitro. Alpha1a, α1b and α1d transcripts were detected by qRT-PCR in proximal and distal CE segments and the α1a and α1d were shown to predominate over the 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<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 non-hormonal approach for male contraception.
- The American Society for Pharmacology and Experimental Therapeutics