Pharmacological characteristics of KP-102 (GHRP-2), a potent growth hormone-releasing peptide.
KP-102 (D-alanyl-3-(2-naphthyl)-D-alanyl-L-alanyl-L-tryptophyl-D-phenylalanyl-L-lysinamide dihydrochloride, growth hormone-releasing peptide-2, GHRP-2, pralmorelin, CAS 158861-67-7), is a potent synthetic growth hormone (GH) secretagogue. In the present study, the pharmacological characteristics of the GH-releasing property of KP-102 were investigated by means of in vivo and in vitro experiments. In conscious rats, the GH-releasing activity of KP-102 was more potent than that of exogenously injected GH-releasing hormone (GHRH). Under pentobarbital anesthesia in which endogenous somatostatin secretion is known to be decreased, KP-102 and GHRH, both showed an almost equivalent GH-releasing potency, which was also similar to that of KP-102 in conscious rats. Besides, KP-102 showed GH-releasing activity in conscious dogs as well, while GHRH failed to increase serum GH levels in conscious dogs. These findings suggest that the GH-releasing activity of KP-102 was less sensitive to GH suppression by endogenous somatostatin as compared with that of GHRH. The GH-releasing activity of KP-102 was completely absent in hypophysectomized rats, but present in median eminence-lesioned rats in which secreted GH amounts were significantly less than those normal rats, indicating necessity of the median eminence (endogenous GHRH) to exert the full activity of KP-102 in GH stimulation. KP-102 directly stimulated GH secretion from cultured rat anterior pituitary cells, although the GH-releasing potency of KP-102 was significantly weaker than that of GHRH in vitro. In conscious rats, KP-102 stimulated the secretion of both adrenocorticotrophic hormone (ACTH) and corticosterone, but not of prolactin. Three weeks administration of KP-102 showed growth-accelerating effect, a slight increase of body weight and wet weight of some organs in both normal and monosodium glutamate (MSG)-treated rats. These results suggest that KP-102 showed specific GH-releasing activity apart from slight ACTH secretion, and that the GH-releasing activity was stable in comparison with that of exogenously injected GHRH.
Doi
Naomi
N
Department of Pharmacology, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., Tokyo, Japan. doi_naomi@kaken.co.jp
Hirotani
Chiharu
C
Ukai
Kiyoharu
K
Shimada
Osafumi
O
Okuno
Tadashi
T
Kurasaki
Shigeru
S
Kiyofuji
Takeshi
T
Ikegami
Reiko
R
Futamata
Machiko
M
Nakagawa
Terutake
T
Ase
Katsuhiko
K
Chihara
Kazuo
K
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000758:Anesthesia; D000818:Animals; D019540:Area Under Curve; D002478:Cells, Cultured; D003345:Corticosterone / Q000097:blood; D004285:Dogs; D013006:Growth Hormone / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006728:Hormones / Q000378:metabolism; D006993:Hypnotics and Sedatives; D007016:Hypophysectomy; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008473:Median Eminence / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D010424:Pentobarbital; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012970:Sodium Glutamate / Q000494:pharmacology
D006728:Hormones; D006993:Hypnotics and Sedatives; D009842:Oligopeptides; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C091874:growth hormone-releasing peptide-2; D010424:Pentobarbital; D012970:Sodium Glutamate; D003345:Corticosterone