title: MT-II induces penile erection via brain and spinal mechanisms.
abstract: alpha-Melanocyte-stimulating hormone induces penile erection via melanocortin (MC) receptors in areas surrounding the third ventricle, but spinal and peripheral mechanisms have not been demonstrated. We used pharmacological strategies to localize the site of the proerectile action of the melanocortin receptor agonist MT-II. We administered MT-II intracerebroventribularly (i.c.v.), intrathecally (i.th.), and intravenously (i.v.) and scored penile erection and yawning for 90 min in awake male rats. In some animals i.c.v. or i.th. SHU-9119 was injected 10 minutes before i.c.v. and i.th. MT-II to confirm the MC receptor action of the agonist and to distinguish spinal from supraspinal effects. To exclude a site of action in the penis, we recorded intracorporal pressure responses to intracavernosal injection of MT-II in the anesthetized rat. MT-II induced penile erections in a dose-dependent fashion, with optimal response at 1 microg for both i.c.v. and i.th. routes. Supraspinal MT-II-induced erections were completely suppressed by 1 microg SHU-9119 i.c.v. Yawning was observed with i.c.v. and i.v. MT-II, whereas spinal injection did not produce this behavior. SHU-9119 blocked the erectile responses to i.th. MT-II when injected i.th. but not i.c.v. Intracavernosal MT-II neither increased intracorporal pressure nor augmented neurostimulated erectile responses. The lumbosacral spinal cord contains MC receptors that can initiate penile erection independent of higher centers. We confirmed the supraspinal proerectile action of MT-II. These results provide insight into the central melanocortinergic pathways that mediate penile erection and may allow for more efficacious melanotropin-based therapy for erectile dysfunction.
authors.affiliation: Department of Urology, University of Washington School of Medicine, Seattle, Washington 98195, USA. wesseks@u.washington.edu
authors.forename: Hunter
authors.initials: H
authors.lastname: Wessells
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
authors.forename: John
authors.initials: J
authors.lastname: Hackett
authors.forename: Guoxia
authors.initials: G
authors.lastname: Han
authors.forename: Preeti
authors.initials: P
authors.lastname: Balse-Srinivasan
authors.forename: Todd W
authors.initials: TW
authors.lastname: Vanderah
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D010410:Penile Erection / Q000187:drug effects*; D051381:Rats; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; C081720:alpha-MSH (4-10)amide, Ac-Nle(4)-cyclo(Asp(5)-Phe(7)-Lys(10))-; D000521:alpha-MSH