Effects in vitro of New Growth Hormone Releasing Peptide (GHRP‐1) on Growth Hormone Secretion from Ovine Pituitary Cells in Primary Culture

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Abstract
Continuous perifusion of pituitary cells was used to study the effects of a newly synthesized GHRP (GHRP-1 or KP 101) on growth hormone (GH) secretion from ovine pituitary cells and these have been compared to effects of growth hormone-releasing factor (GRF) and the original growth hormone-releasing peptide (GHRP-6). GH was continuously released at a constant rate during perifusion and secretion was increased by KP 101, GHRP-6 and GRF in a dose-dependent manner. The half-maximal effective dose of KP 101 and GHRP-6 was 10−7 M, an order of magnitude higher than that for GRF. The maximal effects of KP 101 and GHRP-6 were similar but significantly less than the maximal effect of GRF. Blockade of calcium channels with Cd2+ (2 mM) totally and reversibly abolished the releasing effects of all three peptides. Like GHRP-6, the GH release induced by KP 101 was not affected by a GRF antagonist ([Ac-Tyr1, D-Arg2]-GRF 1–29, 1 μM) which significantly reduced the effect of GRF on GH release. For each peptide, the response to a second application (1 h after the first application) was lower than the first response. When GRF (or KP 101, GHRP-6) was applied first and then KP 101 or GHRP-6 (or GRF) given 1 h later, the second response was not attenuated. Only a small additive effect on the release of GH by GRF was obtained by the co-administration of either KP 101 or GHRP-6. This result was achieved with maximal doses of the peptides, but not with half-maximal doses. These data indicate that KP 101 has similar potency and GH releasing properties to GHRP-6 but both are less potent than GRF. There is no synergistic effect of the peptides with GRF and only a small additive effect of KP 101 or GHRP-6 on GRF-stimulated GH release from ovine pituitary cells in vitro. KP 101 stimulates GH release by a mechanism that involves a common step employed also by GRF and GHRP-6, an increase in calcium influx. In addition, our data strongly suggest that KP 101 like GHRP-6 do not act through the GRF receptor and that there is no cross-desensitization the GRF elicited response.

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