Effects in vitro of new growth hormone releasing peptide (GHRP-1) on growth hormone secretion from ovine pituitary cells in primary culture.
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 microM) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Wu
D
D
Prince Henry's Institute of Medical Research, Clayton (Melbourne), Victoria, Australia.
Chen
C
C
Zhang
J
J
Katoh
K
K
Clarke
I
I
D000595:Amino Acid Sequence; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D012756:Sheep
D002121:Calcium Channel Blockers; D009842:Oligopeptides; D002104:Cadmium; C079956:alanyl-histidyl-(2-naphthyl)alanyl-tryptophyl-phenylalanyl-lysinamide; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone