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 |
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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. |
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ISSN: | 1521-0103 |
DOI: | 10.1124/jpet.117.246710 |