ACTH releasing activity of KP-102 (GHRP-2) in rats is mediated mainly by release of CRF.
KP-102 (GHRP-2: pralmorelin) is a synthetic growth hormone releasing peptide (GHRP) that powerfully stimulates the release of GH by acting (i.v.) at both hypothalamic and pituitary sites. Intravenous (i.v.) administration of KP-102 also elicits slight but significant release of adrenocorticotropic hormone (ACTH) in both animals and humans, as is seen with other GHRPs. GHRPs are thought to stimulate the hypothalamic-pituitary-adrenal axis by releasing endogenous ACTH secretagogues such as arginine vasopressin (AVP) and/or corticotropin releasing factor (CRF), though neither AVP nor CRF has been shown clearly to be involved significantly in GHRP-evoked ACTH release. In the present study, we investigated the effects of KP-102 on ACTH release in conscious rats under improved experimental conditions that minimized the influence of stress. Administration of KP-102 i.v. increased plasma ACTH significantly, but did not stimulate ACTH release from rat primary pituitary cells. Administration of KP-102 together with either AVP or CRF elicited significantly greater increases in plasma ACTH levels than any of the agonists alone. Notably, the combination of KP-102 and AVP produced a much greater increase in ACTH than KP-102 plus CRF, indicating that KP-102 augments the effect of exogenous CRF only weakly. Conversely, a CRF antagonist markedly inhibited KP-102-induced ACTH release in conscious rats, whereas an AVP antagonist or anti-AVP antiserum did not. Taken together, these findings suggest that KP-102 acts via the hypothalamus to stimulate ACTH release in rats, and that these effects are mediated mainly by the release of CRF.
Hirotani
Chiharu
C
Central Research Laboratories, Kaken Pharmaceutical Co. Ltd., 14 Shinomiya Minamikawara-cho, Yamashinaku, Kyoto, 607-8042, Japan. hirotani_chiharu@kaken.co.jp
Oki
Yutaka
Y
Ukai
Kiyoharu
K
Okuno
Tadashi
T
Kurasaki
Shigeru
S
Ohyama
Tadashi
T
Doi
Naomi
N
Sasaki
Ken
K
Ase
Katsuhiko
K
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000502:physiology; D002469:Cell Separation; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000502:physiology*; D004357:Drug Synergism; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D009842:Oligopeptides; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C091874:growth hormone-releasing peptide-2