Oxytocin-induced contractions within rat and rabbit ejaculatory tissues are mediated by vasopressin V1A receptors and not oxytocin receptors.
OBJECTIVE
Oxytocin is believed to be involved in ejaculation by increasing sperm number and contracting ejaculatory tissues. However, oxytocin may mediate these effects via oxytocin or vasopressin (AVP) receptors. The aim of this study was to determine the effect of oxytocin and AVP on peripheral tissues involved in ejaculation and to identify the receptor subtype(s) involved.


METHODS
Standard tissue bath techniques were used to measure isometric tension from tissues involved in ejaculation and erection.


RESULTS
Oxytocin and AVP failed to elicit a tonic contractile response in rat and rabbit testes, vas deferens, epididymis, seminal vesicles and prostate. In contrast, oxytocin and AVP elicited large tonic contractions in erectile (corpus spongiosum and corpus cavernosum) and ejaculatory (prostatic urethra, bladder neck and ejaculatory duct) tissues in a concentration-dependent manner. The selective oxytocin agonist, [Thr4,Gly7]-oxytocin and the V2 agonist, [deamino-Cys1,Val4,D-Arg8]-vasopressin (dDAVP), failed to contract tissues. Oxytocin and AVP-induced contractions were weakly antagonized by the selective oxytocin antagonist, L-368899 but potently antagonized by the V1A antagonist, SR49059. The V1B antagonist SSR149415 failed to antagonize AVP contractions except in rabbit bladder neck. Neither L-368899 nor SR49059 antagonized endothelin-1-induced contractions.


CONCLUSIONS
The contractile effect of oxytocin on rat and rabbit ejaculatory and erectile tissues is mediated via V1A receptors. Endothelin-1-induced contractions are not due to endogenous oxytocin or AVP release. V1A receptor antagonists may have a therapeutic role in both erectile dysfunction and premature ejaculation.
Discovery Biology, Pfizer Global Research & Development, Sandwich, Kent, UK.
J
J
Gupta
Rj
R
Russell
Cp
C
Wayman
D
D
Hurley
Vm
V
Jackson
D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004542:Ejaculation / Q000187:drug effects; D019332:Endothelin-1 / Q000378:metabolism; D005837:Genitalia, Male / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism*; D014521:Urethra / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism
D019332:Endothelin-1; D006727:Hormone Antagonists; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D010121:Oxytocin