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ACTH releasing activity of KP-102 (GHRP-2) in rats is mediated mainly by release of CRF

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Abstract

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.

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Authors and Affiliations

  1. Central Research Laboratories, Kaken Pharmaceutical Co. Ltd., 14 Shinomiya Minamikawara-cho, Yamashinaku, Kyoto, 607-8042, Japan

    Chiharu Hirotani, Kiyoharu Ukai, Tadashi Okuno, Shigeru Kurasaki & Tadashi Ohyama

  2. Second Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan

    Yutaka Oki

  3. Kaken Pharmaceutical Co. Ltd., 2-28-8, Honkomagome, Bunkyo-ku, Tokyo, 113-8650, Japan

    Naomi Doi, Ken Sasaki & Katsuhiko Ase

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  1. Chiharu Hirotani
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Correspondence to Chiharu Hirotani.

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Hirotani, C., Oki, Y., Ukai, K. et al. ACTH releasing activity of KP-102 (GHRP-2) in rats is mediated mainly by release of CRF. Naunyn-Schmiedeberg's Arch Pharmacol 371, 54–60 (2005). https://doi.org/10.1007/s00210-004-1009-3

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  • DOI: https://doi.org/10.1007/s00210-004-1009-3

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