Melanotan-II: Investigation of the inducer and facilitator effects on penile erection in anaesthetized rat.
The effects of melanotan-II, a non-specific agonist of melanocortin receptors, on erection and its possible sites of action were investigated in anesthetized rats. Delivered i.v. (0.1, 0.3 and 1 mg/kg) or within the paraventricular nucleus of the hypothalamus (0.1 and 1 microg), melanotan-II exerted a dose-dependent inducer activity on erection by eliciting erectile events and shortening latency of the first erectile event to occur. Erectile events were of higher amplitude in rats treated with melanotan-II i.t. (0.2 microg) delivered at the L6-S1 level than in animals treated with the vehicle i.t. delivered. Erectile responses elicited by cavernous nerve stimulation were increased after i.v. melanotan-II (1 mg/kg), thereby exerting facilitator effect on erection. In contrast, melanotan-II injected within the corpus cavernosum (1 microg) did not display any facilitator activity. To investigate the neural pathways involved in the facilitator effect of melanotan-II, we performed acute spinalization (T8 level) and differential selective nerve transections. Neither spinalization nor bilateral transection of pelvic nerves or dorsal penile nerves impaired facilitator activity of i.v. melanotan-II (1 mg/kg). Conversely, the facilitator effect of melanotan-II was abolished after acute removal of the lumbar paravertebral sympathetic chain. These results lead to the conclusion that central and peripheral melanocortin pathways are recruited by melanotan-II, depending on its route of delivery, to exert both inducer and facilitator activities on erection.
Giuliano
F
F
Pelvipharm Laboratories, CNRS, Bat 5, avenue de la Terrasse, 91190 Gif-sur-Yvette, France. giuliano@cyber-sante.org
Clément
P
P
Droupy
S
S
Alexandre
L
L
Bernabé
J
J
D000758:Anesthesia; D000818:Animals; D003655:Decerebrate State / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007267:Injections; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D009415:Nerve Net / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D010413:Penis / Q000098:blood supply / Q000294:innervation; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D010456:Peptides, Cyclic; C079282:melanotan-II; D000521:alpha-MSH