Serotonin Induces a Biphasic Response in Rabbit Cavernosal Smooth Muscle: Relevance to the Erectile Process

Abstract

Introduction: Serotonin (5-hydroxytryptamine; 5-HT) can cause contraction in cavernosal smooth muscle. We further evaluated this effect of 5-HT. Methods: Organ bath studies were used. Results: 5-HT induced a sustained contraction occasionally accompanied by a transient relaxation (in 30% of rabbit cavernosal tissues) that preceded the contraction. Ondansetron and Y-25130 (both 5-HT₃ receptor antagonists) but not SB-269970 (a 5-HT₇ receptor antagonist) significantly inhibited or abolished this transient relaxation. Doxazosin (dox, an α₁-receptor antagonist) and ketanserin (ketan, a 5-HT_2A receptor antagonist) significantly inhibited or abolished the sustained contraction. The effects of dox on 5-HT-mediated contraction were concentration-dependent. Conclusions: Our findings further confirm that the peripheral serotonergic pathway may play a part in the erectile process via 5-HT_2A receptor-mediated contractile and 5-HT₃ receptor-mediated relaxant activities. Our results also support the findings of human studies, which suggest that both ketan and dox may exert beneficial effects on the erectile process.

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

“…Furthermore, 5-HT 1A , 5-HT 2A , and 5-HT 4 receptors were implicated in human erection Lau et al, 2006). Lau et al (2007) further confirmed that the peripheral 5-HT pathway may play a part in the erectile process via 5-HT 2A receptor-mediated contractile and 5-HT 3 receptor-mediated relaxant activities. Thus, it cannot be excluded that 5-HT, released from penile nerves, is a contractile neurotransmitter in the erectile process, the importance of which has to be established.…”

Are 5‐HT3 antagonists effective in obsessive–compulsive disorder? A systematic review of literature

“…the most favourable, but again dose equivalences and SSRI co‐administration should be considered; Soltani et al ., ). Among side effects, constipation, headache and dry mouth predominated, whereas sexual disorders/dysfunctions were found in the two combination studies involving co‐administration of SSRIs; this was an expected effect for this class of antidepressants, so we believe that it is unlikely that they would represent a side effect of 5‐HT 3 receptor antagonists, although interactions are possible; in fact, ondansetron and other 5‐HT 3 receptor antagonists were shown to interfere with animal erectile activity in conjunction with other serotonergic and dopaminergic mechanisms (Maeda et al ., , ; Lau et al ., ). Overall, the adverse symptom pattern mimicked the one described for patients with neoplastic diseases treated for chemotherapy‐induced nausea, except for headache being less common than constipation (Goodin and Cunningham, ).…”

Nonischaemic priapism associated with selective serotonin-3 receptor antagonist

“…At the penile level, several studies demonstrated the role of the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4 receptors in the erectile process (Lau et al, 2007). The authors demonstrated that the transient relaxation of cavernosal smooth muscle is inhibited by ondansetron by 100%.…”

“…In the literature, it is shown that ondansetron reduced haloperidol and antipsychotic induced extrapyramidal symptoms (EPS; Hirafuji, 2013). Lau, Thompson, Mumtaz, Morgan, and Mikhailidis (2007) demonstrated the inhibitor effect of ondansetron on cavernosal smooth muscle contraction. Lau, Thompson, Mumtaz, Morgan, and Mikhailidis (2007) demonstrated the inhibitor effect of ondansetron on cavernosal smooth muscle contraction.…”

“…The relaxation of cavernosal smooth muscle and the smooth muscles of the arteriolar and arterial walls play a key role in the erection (Dean & Lue, 2005). Lau, Thompson, Mumtaz, Morgan, and Mikhailidis (2007) demonstrated the inhibitor effect of ondansetron on cavernosal smooth muscle contraction.…”