Identification, localization and functional in vitro and in vivo activity of oxytocin receptor in the rat penis

Abstract

We recently found that the oxytocin receptor (OTR) is expressed in the human and rabbit corpus cavernosum and mediates contractility in vitro. The present study extended our investigations to the rat, and explored whether OTR regulates penile detumescence in vivo. Real-time RT-PCR quantitatively characterized the distribution of OTR mRNA in the male genital tract. Specific transcripts for OTR were expressed in all the tissues investigated. Penile expression of OTR was comparable to that observed in testis and prostate. Western blot analysis detected a single band of the expected molecular mass for OTR in all tissues examined, including rat penis. Expression of OTR protein in rat penile extracts was further confirmed by binding studies, using the OTR selective radiolabeled ligand 125 I-OTA (K d =17 6·5 pM, B max =15·7 5 fmoles/mg protein). OTR was immunolocalized to the endothelial and smooth muscle compartments of cavernous spaces and blood vessels. In rat corpus cavernosum strips, oxytocin (OT) and an OTR selective agonist ([Thr 4 ,Gly 7 ]OT) induced identical increases in tension, while different vasopressin agonists were less active. In vivo, OT intracavernous injection (ICI) dose-dependently inhibited intracavernous pressure (ICP) increase elicited by either electrical stimulation of the cavernous nerve or ICI of papaverine with similar IC 50 s (117·7 37 mU). The OTR antagonist, atosiban, counteracted the contractile effect of OT both in vitro and in vivo. Atosiban alone significantly increased ICP at lower stimulation frequencies (2 Hz=P<0·001 and 4 Hz=P<0·05 vs control), but not at the maximal frequency (16 Hz). Our data showed that OTR is present in the rat penis and mediates contractility both in vitro and in vivo, therefore suggesting a role for OT in maintaining penile detumescence.

Oxytocin Immunoreactivity in the Corpus Cavernosum of Patients with Erectile Dysfunction

“…Some studies also detected similar oxytocin receptor tissue staining characteristics [7,8] . We used as the sole method immunohistochemistry with a semiquantitative analysis.…”

“…The possibility that a periorgasmic increase in oxytocin contributes to the termination of the erection peripherally should also be considered. This idea was supported by the presence of oxytocin receptor gene expression in the human corpus cavernosum [7] , and contractile activity of oxytocin on the smooth muscle of the corpus cavernosum [6][7][8] .…”

“…Zhang et al [8] reported that intracavernosal administration of oxytocin in rats inhibited intracavernous pressure increase. However, the results of animal studies cannot always be extrapolated to humans.…”

“…Vignozzi et al [7] later reported that the oxytocin receptor gene and protein are expressed by rabbit and human corpus cavernosum and that they mediate contractility. Zhang et al [8] also found that the oxytocin receptor exists in rat corpus cavernosum and mediates contractility both in vitro and in vivo. They suggested that oxytocin is generated locally in the penile tissue exerting an autocrine/paracrine role in regulating cavernous smooth muscle tone.…”

Pathophysiology of Lifelong Premature Ejaculation

“…In recent years, research into oxytocinergic, dopaminergic and endocrinological factors related to PE has been conducted by a number of research groups (16,(44)(45)(46)(47)(48). However, their attention has not been directed to the hypertonic state of lifelong PE.…”