1. Contraction of Rat Cauda Epididymis Smooth Muscle to α 1 -Adrenoceptor Activation Is Mediated by α 1A -Adrenoceptors.
- Author
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Pacini ESA, Castilho ACS, Hebeler-Barbosa F, Pupo AS, and Kiguti LRA
- Subjects
- Adrenergic alpha-1 Receptor Antagonists pharmacology, Animals, Epididymis drug effects, Gene Expression Regulation drug effects, Male, Muscle, Smooth drug effects, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Receptors, Adrenergic, alpha-1 genetics, Epididymis physiology, Muscle Contraction drug effects, Muscle, Smooth physiology, Receptors, Adrenergic, alpha-1 metabolism
- 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 α
1 -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 [3 H]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 (p KB ≈ 9.50) and 5-methylurapidil (p KB ≈ 9.0) and with low affinity by BMY 7378 (p KB ≈ 7.0) and the α1B -selective L-765,314 (p A2 < 7.0), suggesting contractions are mediated by α1A -ARs. The clinically used α1A/D -ARs antagonist tamsulosin potently (p A2 ≈ 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., (Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.)- Published
- 2018
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