Vergoni A V, Bertolini A, Mutulis F, Wikberg J E, Schiöth H B
Department of Biomedical Sciences, University of Modena, Italy.
Eur J Pharmacol. 1998 Dec 4;362(2-3):95-101. doi: 10.1016/s0014-2999(98)00753-5.
We injected i.c.v. the natural agonist alpha-MSH (melanocyte-stimulating hormone) and the first selective melanocortin MC4 receptor antagonist HS014 (cyclic [AcCys11, D-Nal14, Cys18, Asp-NH(2)22]-beta-MSH(11-22) in rats and scored a number of behavioral effects which have been related to the melanocortic peptides. The results showed that HS014 (5 microg/rat) completely blocked alpha-MSH (3 and 5 microg/rat)-induced grooming, yawning and stretching. Penile erections induced by alpha-MSH were, however, only partially blocked by HS014. Injections of alpha-MSH decreased food intake in food-deprived rats, whereas HS014 increased food intake. When the peptides were given together, the food intake was similar to that of saline treated controls. Locomotion/exploration and resting were not influenced by either peptide. Our data show that exogenous beta-MSH decreases food intake, and that an endogenous central melanocortinergic inhibitory tone on feeding prevails which can be blocked with HS014, leading to an increase in food intake. Our data also provide evidence that grooming, stretching and yawning in rats may be mediated by the melanocortin MC4 receptor, whereas penile erections might perhaps be mediated by some other melanocortin receptor.
我们向大鼠脑室内注射了天然激动剂α-促黑素（α-MSH，黑素细胞刺激激素）和首个选择性黑素皮质素MC4受体拮抗剂HS014（环[AcCys11，D-Nal14，Cys18，Asp-NH(2)22]-β-MSH(11-22)），并对一些与黑素皮质肽相关的行为效应进行了评分。结果显示，HS014（5微克/只大鼠）完全阻断了α-MSH（3微克/只大鼠和5微克/只大鼠）诱导的梳理毛发、打哈欠和伸展身体行为。然而，HS014仅部分阻断了α-MSH诱导的阴茎勃起。注射α-MSH可减少饥饿大鼠的食物摄入量，而HS014则增加食物摄入量。当同时给予这两种肽时，食物摄入量与生理盐水处理的对照组相似。两种肽对运动/探索行为和静息行为均无影响。我们的数据表明，外源性β-MSH可减少食物摄入量，且存在一种内源性中枢黑素皮质素能对进食的抑制性调节，这种调节可被HS014阻断，从而导致食物摄入量增加。我们的数据还提供了证据，表明大鼠的梳理毛发、伸展身体和打哈欠行为可能由黑素皮质素MC4受体介导，而阴茎勃起可能由其他一些黑素皮质素受体介导。
