Bagnasco Michela, Tulipano Giovanni, Melis Maria R, Argiolas Antonio, Cocchi Daniela, Muller Eugenio E
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Via Vanvitelli, 32-20129 Milan, Italy.
Regul Pept. 2003 Mar 28;111(1-3):161-7. doi: 10.1016/s0167-0115(02)00283-5.
Ghrelin, a circulating growth-hormone releasing peptide derived from stomach, stimulates food intake through neuropeptide Y (NPY) neurons of the arcuate nucleus in the hypothalamus (ARC). We examined the effect of ghrelin microinjected into the ARC and the influence of intracerebroventricular (i.c.v.) pretreatment with a GHRH or NPY receptor antagonist on ghrelin-induced food intake in free-feeding male rats. Ghrelin (0.1-1 microg) stimulated food intake in a dose-dependent manner, and this effect was reduced by 55-60% by the Y(5) NPY receptor antagonist (10 microg i.c.v.), but not by the GHRH receptor antagonist MZ-4-71 (10 microg i.c.v.). We also evaluated the effects of passive ghrelin immunoneutralization by the microinjection of anti-ghrelin immunoglobulins (IgGs) intracerebroventricularly or directly into the ARC on food intake in free-feeding and fasted male rats. i.c.v. administration of anti-ghrelin IgGs decreased cumulative food intake over 24 h, whereas microinfusion of anti-ghrelin IgGs into the ARC induced only a short-lived (2 and 6 h) effect. Collectively, these data would indicate that centrally derived ghrelin has a major role in the control of food intake in rats and, in this context, blood-born ghrelin would be effective only in relation to its ability to reach the ARC, which is devoid of blood-brain barrier.
胃饥饿素是一种源自胃的循环生长激素释放肽，它通过下丘脑弓状核的神经肽Y（NPY）神经元刺激食物摄入。我们研究了向弓状核微量注射胃饥饿素的效果，以及脑室注射生长激素释放激素（GHRH）或NPY受体拮抗剂对自由进食雄性大鼠胃饥饿素诱导的食物摄入的影响。胃饥饿素（0.1 - 1微克）以剂量依赖的方式刺激食物摄入，Y(5) NPY受体拮抗剂（脑室注射10微克）可使这种作用降低55 - 60%，但GHRH受体拮抗剂MZ - 4 - 71（脑室注射10微克）则无此作用。我们还评估了通过脑室注射或直接向弓状核微量注射抗胃饥饿素免疫球蛋白（IgG）对自由进食和禁食雄性大鼠食物摄入的被动胃饥饿素免疫中和作用。脑室注射抗胃饥饿素IgG可降低24小时内的累积食物摄入量，而向弓状核微量注射抗胃饥饿素IgG仅诱导短暂（2小时和6小时）的作用。总体而言，这些数据表明，中枢来源的胃饥饿素在大鼠食物摄入控制中起主要作用，在此背景下，血液循环中的胃饥饿素仅在其能够到达缺乏血脑屏障的弓状核时才有效。
