Wessells H, Hruby V J, Hackett J, Han G, Balse-Srinivasan P, Vanderah T W
Department of Urology, University of Washington School of Medicine, Harborview Medical Center, 325 Ninth Avenue, Seattle, WA 98195, USA.
Neuroscience. 2003;118(3):755-62. doi: 10.1016/s0306-4522(02)00866-7.
Penile erection induced by alpha-melanocyte-stimulating hormone and melanocortin receptors (MC-R) in areas of the spinal cord and periphery has not been demonstrated. To elucidate sites of the proerectile action of melanocortin peptides, in awake male rats we administered the MC-R agonist Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH(2) (MT-II) i.c.v., intrathecal (i.th.) and i.v. and scored penile erection and yawning. Injection of the MC-R antagonist Ac-Nle-c[Asp-His-DNal(2')-Arg-Trp-Lys]-NH(2) (SHU-9119) i.c.v. or i.th. in combination with i.th. MT-II differentiated spinal from supraspinal effects. To exclude a site of action in the penis, we recorded intracavernous pressure responses to intracavernosal injection of MT-II in the anesthetized rat.I.c.v., i.th., and i.v. MT-II induced penile erections in a dose-dependent fashion. Yawning was observed with i.c.v. and i.v. MT-II, while spinal injection did not produce this behavior. Intrathecal delivery of MT-II to the lumbosacral spinal cord was more efficacious in inducing erections than i.c.v. or i.v. administration; 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 intracavernous pressure nor augmented neurostimulated erectile responses. We confirmed the central proerectile activity of MT-II and demonstrated that in addition to a site of action in the brain, the distal spinal cord contains melanocortin receptors that can initiate penile erection independent of higher centers. These results provide new insight into the central melanocortinergic pathways that mediate penile erection and may allow for more efficacious melanotropin-based therapy for erectile dysfunction.
α-黑素细胞刺激素及黑素皮质素受体（MC-R）在脊髓和外周区域诱导阴茎勃起的现象尚未得到证实。为阐明黑素皮质素肽促勃起作用的位点，我们对清醒雄性大鼠进行脑室内（i.c.v.）、鞘内（i.th.）和静脉内（i.v.）注射MC-R激动剂Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH₂（MT-II），并对阴茎勃起和打哈欠进行评分。脑室内或鞘内注射MC-R拮抗剂Ac-Nle-c[Asp-His-DNal(2')-Arg-Trp-Lys]-NH₂（SHU-9119）并联合鞘内注射MT-II，可区分脊髓和脊髓以上的效应。为排除阴茎中的作用位点，我们记录了麻醉大鼠海绵体内注射MT-II后的海绵体内压反应。脑室内、鞘内和静脉内注射MT-II均以剂量依赖方式诱导阴茎勃起。脑室内和静脉内注射MT-II时可观察到打哈欠，而脊髓注射则不产生此行为。与脑室内或静脉内给药相比，向腰骶部脊髓鞘内递送MT-II诱导勃起更有效；鞘内注射SHU-9119可阻断对鞘内注射MT-II的勃起反应，但脑室内注射则无此作用。海绵体内注射MT-II既不增加海绵体内压，也不增强神经刺激引起的勃起反应。我们证实了MT-II的中枢促勃起活性，并证明除了在脑内有作用位点外，脊髓远端也含有黑素皮质素受体，可独立于高级中枢启动阴茎勃起。这些结果为介导阴茎勃起的中枢黑素皮质素能通路提供了新的见解，并可能使基于促黑素的勃起功能障碍治疗更有效。
