EFFECTS OF THE SYNTHESIZED GROWTH-HORMONE RELEASING PEPTIDE, KP-102, ON GROWTH-HORMONE RELEASE IN SODIUM GLUTAMATE MONOHYDRATE-TREATED LOW GROWTH RATS

KP-102 (D-Ala-D-beta-Nal-Ala-Trp-D-Phe-Lys-NH2), a new second generati on hexapeptide, has a potent growth hormone (GH)-releasing action in v ivo and in vitro. Here, we evaluated the GH-releasing action of KP-102 under pentobarbital (PB) anesthesia in neonatally sodium-glutamate-mo nohydrate-treated low growth (NMSG-LG) rats. The plasma GH level in NM SG-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 relea sing 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). W hen 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-1 02 at 2 mu g i.c.v. also increased the plasma GH levels (p<0.01) to ab out 1/8.3 (95% C.L. 1/22.7 - 1/3.1) of that by systematic administrati on, 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 th e GH release by a direct or indirect antagonism of somatostatin (SRIF) and growth hormone releasing hormone (GHRH) release in the hypothalam us and by a direct action on the pituitary. Furthermore, the GH-releas ing action of KP-102 was similar and additive upon both regions in viv o at the maximum effective dose. Moreover, since the GH-release in res ponse to KP-102 administration differed between NMSG-LG and normal rat s, 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.