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首页> 外文期刊>Life sciences >EFFECTS OF THE SYNTHESIZED GROWTH HORMONE RELEASING PEPTIDE, KP-102, ON GROWTH HORMONE RELEASE IN SODIUM GLUTAMATE MONOHYDRATE-TREATED LOW GROWTH RATS
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EFFECTS OF THE SYNTHESIZED GROWTH HORMONE RELEASING PEPTIDE, KP-102, ON GROWTH HORMONE RELEASE IN SODIUM GLUTAMATE MONOHYDRATE-TREATED LOW GROWTH RATS

机译：合成的生长激素释放肽KP-102对谷氨酸钠一水合处理的低生长大鼠生长激素释放的影响

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KP-102 (D-Ala-D-beta-Nal-Ala-Trp-D-Phe-Lys-NH2), a new second generation hexapeptide, has a potent growth hormone (GH)-releasing action in vivo and in vitro. Here, we evaluated the GH-releasing action of KP-102 under pentobarbital (PB) anesthesia in neonatally sodium-glutamate-monohydrate-treated low growth (NMSG-LG) rats. The plasma GH level in NMSG-LG rats after i.v. administration of KP-102 at 100 mu g/kg was 1/6.7 (95% C.L. 1/14.7 - 1/3.0) of that in normal rats given the same dose (p<0.01). However, the increase was significant compared with that in normal rats after saline administration (p<0.01). The plasma GH releasing action of KP-102 at 100 mu g/kg i.v. in rats with lesions in the bilateral hypothalamic arcuate nuclei (ARC), was about 1/6.3 (95% C.L. 1/12.4 - 1/3.2) of that in normal rats under PB anesthesia(p<0.01). When KP-102 was injected into the ARC at doses of 0.0002, 0.02 and 2 mu g/rat, GH release was dose-related (p<0.01) under PB anesthesia. KP-102 at 2 mu g i.c.v. also increased the plasma GH levels (p<0.01) to about 1/8.3 (95% C.L. 1/22.7 - 1/3.1) of that by systematic administration, at the same potency as the ARC injection (1/13.7 and 95% C.L. 1/37.2 - 1/5.0). These findings suggest that KP-102 potently stimulates the GH release by a direct or indirect antagonism of somatostatin (SRIF) and growth hormone releasing hormone (GHRH) release in the hypothalamus and by a direct action on the pituitary. Furthermore, the GH-releasing action of KP-102 was similar and additive upon both regions in vivo at the maximum effective dose. Moreover, since the GH-release in response to KP-102 administration differed between NMSG-LG and normal rats, and since KP-102 increased the GH release even in NMSG-LG rats, it should be evaluated in the hypophysial GH secretion tests, and may be used to treat the hypophysial GH secretion insufficiency. [References: 20]
机译：新的第二代六肽KP-102（D-Ala-D-β-Nal-Ala-Trp-D-Phe-Lys-NH2）在体内和体外具有有效的生长激素（GH）释放作用。在这里，我们评估了戊巴比妥（PB）麻醉下新生谷氨酸钠一水合物治疗的低生长（NMSG-LG）大鼠中KP-102的GH释放作用。静脉注射后NMSG-LG大鼠血浆GH水平给予相同剂量的正常大鼠KP-102的100μg / kg剂量是正常大鼠的1 / 6.7（95％C.L. 14.7-1 / 3.0）（p <0.01）。但是，与生理盐水给药后的正常大鼠相比，该增加显着（p <0.01）。 KP-102在100μg / kg静脉内的血浆GH释放作用。在PB麻醉下，双侧下丘脑弓状核（ARC）病变的大鼠中，其含量约为正常大鼠的1 / 6.3（95％C.L. 1 / 12.4-1 / 3.2）（p <0.01）。当将KP-102以0.0002、0.02和2μg /大鼠的剂量注射到ARC中时，在PB麻醉下GH的释放与剂量有关（p <0.01）。 i.c.v. 2 g的KP-102还可以通过系统给药将血浆GH水平（p <0.01）提高到血浆GH水平的1 / 8.3（95％CL 1 / 22.7-1 / 3.1），效力与ARC注射相同（1 / 13.7和95％CL 1 / 37.2-1 / 5.0）。这些发现表明，KP-102通过生长抑素（SRIF）和下丘脑中的生长激素释放激素（GHRH）释放的直接或间接拮抗作用以及对垂体的直接作用来有效刺激GH释放。此外，KP-102的GH释放作用相似，并且以最大有效剂量在体内两个区域相加。此外，由于NMSG-LG与正常大鼠对KP-102的反应所释放的GH有所不同，并且KP-102即使在NMSG-LG大鼠中也增加了GH的释放，因此应在垂体GH分泌试验中进行评估，并可用于治疗垂体生长激素分泌不足。 [参考：20]

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