ON THE ACTIONS OF THE GROWTH HORMONE-RELEASING HEXAPEPTIDE, GHRP
ON THE ACTIONS OF THE GROWTH HORMONE-RELEASING HEXAPEPTIDE, GHRP
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DOI：
10.1210/endo-128-4-2027
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发表时间：
1991-04-01
期刊：
影响因子：
4.8
通讯作者：
BADGER, TM
中科院分区：
文献类型：
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作者：
BOWERS, CY;SARTOR, AO;BADGER, TM
生长激素释放肽（组氨酸 - D - 色氨酸 - 丙氨酸 - 色氨酸 - D - 苯丙氨酸 - 赖氨酸 - 氨或GHRP）通过在下丘脑和垂体上独特且互补的双作用位点释放生长激素。这些作用是通过大鼠体内非生长激素释放激素（非GHRH）和非阿片受体介导的。已知某些类型的阿片类物质通过下丘脑作用位点释放生长激素，因此，本研究中使用的皮啡肽七肽和苯并吗啡喃阿片激动剂2549可能作用于下丘脑以释放生长激素。皮啡肽和2549都不会通过直接的垂体作用在体外释放生长激素或增强GHRP或GHRH的生长激素反应，然而GHRH抗血清在体内抑制皮啡肽和2549的生长激素反应（见下文）。有证据表明，这些阿片类物质和GHRP一起协同释放生长激素，这表明了GHRP和阿片类物质的独立作用。目前的数据表明，皮啡肽、2549和GHRP作用的主要差异之一是阿片类物质抑制生长抑素（SRIF）的释放，而GHRP不会。尽管皮啡肽、2549和GHRP对生长激素释放的作用依赖于GHRH，但内源性GHRH的释放并不能解释这些肽组合如何协同释放生长激素。有人提出，皮啡肽/2549与GHRP或GHRH协同释放生长激素是因为这些阿片类物质抑制了SRIF的释放。由于GHRP加GHRH协同的生长激素释放不能用抑制SRIF或刺激GHRH来解释，因此提出了一种替代机制来解释GHRP如何与GHRH协同释放生长激素。GHRP、GHRH和皮啡肽或GHRP、GHRH和2549在释放生长激素方面互补且相当显著的协同相互作用再次有力地支持了这些化合物的独立作用。
GH-releasing peptide (His-DTrp-Ala-Trp-DPhe-Lys-NH2 or GHRP) releases GH by a unique and complementary dual site of action on the hypothalamus and pituitary. These effects are mediated via non-GH-releasing hormone (non-GHRH) and nonopiate receptors in rats.Select types of opiates are known to release GH by a hypothalamic site of action, and thus, the dermorphin heptapeptide and benzomorphan opiate agonist 2549 used in this study presumably act on the hypothalamus to release GH. Neither dermorphin nor 2549 release GH or augmented the GH responses of GHRP or GHRH in vitro by a direct pituitary action, while GHRH antiserum inhibited the GH response of both dermorphin and 2549 in vivo (see below). Evidence indicates that these opiates and GHRP administered together synergistically release GH, demonstrating the independent action(s) of GHRP and the opiates. Present data indicate that one of the major differences in the actions of dermorphin, 2549, and GHRP is the inhibition of somatostatin (SRIF) release by the opiates but not by GHRP. Although the actions of dermorphin, 2549, and GHRP on GH release are GHRH dependent, release of endogenous GHRH does not explain how GH is released synergistically by the combination of these peptides. It is proposed that dermorphin/2549 synergistically release GH with GHRP or GHRH because these opiates inhibit SRIF release. Since the GHRP plus GHRH synergistic GH release was not explained by inhibition of SRIF or stimulation of GHRH, an alternative mechanism is proposed to explain how GHRP synergistically releases GH in combination with GHRH. The complementary, rather dramatic synergistic interaction of GHRP, GHRH, and dermorphin or GHRP, GHRH, and 2549 in releasing GH again strongly supports the independent actions of these compounds.