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504365 
Journal Article 
Effects of the synthesized growth hormone releasing peptide, KP-102, on growth hormone release in sodium glutamate monohydrate-treated low growth rats (vol 59, pg 705, 1996) 
Nakagawa, T; Ukai, K; Ohyama, T; Koida, M; Okamura, H 
2005 
1 
Life Sciences
ISSN: 0024-3205
EISSN: 1879-0631 
76 
23 
2751-+ 
English 
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% CL. 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. (c) 2005 Elsevier Inc. All rights reserved. 
(ghrp-6)-induced gh secretion; hypothalamopituitary disconnection; monosodium glutamate; somatostatin; hexapeptide; pituitary; invitro; ghrp-6