Torsello A, Locatelli V, Melis M R, Succu S, Spano M S, Deghenghi R, Müller E E, Argiolas A
Department of Experimental and Environmental Medicine and Biotechnologies, University of Milano-Bicocca, Italy.
Neuroendocrinology. 2000 Dec;72(6):327-32. doi: 10.1159/000054601.
We have previously reported that hexarelin and some of its analogs, including EP 50885, stimulated GH secretion and feeding after systemic administration in the rat, whereas EP 40904 selectively stimulated food intake and EP 40737 only GH release. The precise mechanism of growth hormone-releasing peptides (GHRPs) actions is still unclear, but the integrity of the arcuate nucleus of the hypothalamus (ARC) appears crucial for their endocrine effects. To better characterize the site(s) and mechanisms(s) of the orexigenic action of GHRPs, we have investigated their effects after infusion into the arcuate, paraventricular, ventromedial and medial preoptic areas of the hypothalamus. Food intake was measured for 60 min following injection of the test compound (2 microg/rat). Hexarelin, EP 40904 and EP 50885 had significant orexigenic effects after injection into the ARC. A specific NPY antagonist significantly inhibited the effect of hexarelin, whereas a GHRH antagonist was ineffective. In the paraventricular nucleus, only EP 50885 stimulated feeding, whereas all peptides were ineffective in the ventromedial nucleus and medial preoptic area. Taken altogether, these results demonstrate that GHRPs are endowed with site-specific orexigenic actions and that endogenous NPY, but not GHRH, mediates these effects. The additional orexigenic action of EP 50885 in the paraventricular nucleus suggests the existence of a GHRP receptor subtype different from the already cloned one.
我们之前曾报道，六氢瑞林及其一些类似物，包括EP 50885，在大鼠全身给药后可刺激生长激素（GH）分泌和进食，而EP 40904选择性地刺激食物摄入，EP 40737仅刺激GH释放。生长激素释放肽（GHRPs）作用的确切机制仍不清楚，但下丘脑弓状核（ARC）的完整性似乎对其内分泌作用至关重要。为了更好地表征GHRPs促食欲作用的位点和机制，我们研究了将它们注入下丘脑的弓状核、室旁核、腹内侧核和视前内侧区后的作用。在注射测试化合物（2微克/大鼠）后60分钟测量食物摄入量。六氢瑞林、EP 40904和EP 50885注入ARC后具有显著的促食欲作用。一种特异性神经肽Y（NPY）拮抗剂显著抑制六氢瑞林的作用，而生长激素释放激素（GHRH）拮抗剂则无效。在室旁核中，只有EP 50885刺激进食，而所有肽在腹内侧核和视前内侧区均无效。综上所述，这些结果表明GHRPs具有位点特异性促食欲作用，并且内源性NPY而非GHRH介导这些作用。EP 50885在室旁核中的额外促食欲作用表明存在一种不同于已克隆的GHRP受体亚型。
