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 -adrenoceptors ( -ARs) plays a key role during the seminal emission phase of ejaculation and -AR antagonism has been suggested as a...

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Veröffentlicht in:The Journal of pharmacology and experimental therapeutics 2018-07, Vol.366 (1), p.21
Hauptverfasser: Pacini, Enio S A, Castilho, Anthony C S, Hebeler-Barbosa, Flavia, Pupo, André S, Kiguti, Luiz R A
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Sprache:eng
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Zusammenfassung: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 -adrenoceptors ( -ARs) plays a key role during the seminal emission phase of ejaculation and -AR antagonism has been suggested as a nonhormonal and reversible male contraceptive target. Since the -AR subtype mediating contraction of rat CE is not known, this study investigates the expression and role of -AR subtypes on the proximal and distal rat CE duct contraction to norepinephrine in vitro. Alpha , , and transcripts were detected by real-time quantitative polymerase chain reaction in proximal and distal CE segments and and were shown to predominate over The inhibition of [ H]prazosin specific binding to intact CE segments from proximal and distal CE by RS 100329 and 5-methylurapidil ( -selective) and BMY 7378 ( -selective) showed that - and -ARs are expressed at similar densities. Norepinephrine-induced contractions of CE were competitively antagonized with high affinity by RS 100329 (p ≈ 9.50) and 5-methylurapidil (p ≈ 9.0) and with low affinity by BMY 7378 (p ≈ 7.0) and the -selective L-765,314 (p < 7.0), suggesting contractions are mediated by -ARs. The clinically used -ARs antagonist tamsulosin potently (p ≈ 10.0) inhibited the norepinephrine-induced CE contractions. Altogether, our results show that - and -ARs are expressed in the CE duct and -AR is the main subtype mediating contraction to norepinephrine. Our results highlight the importance of -AR in the peripheral control of ejaculation and strengthen the -AR as a target for a nonhormonal approach to male contraception.
ISSN:1521-0103
DOI:10.1124/jpet.117.246710