EFFECT OF SUBSTANCE-P BOMBESIN ANTAGONISTS ON THE RELEASE OF GROWTH-HORMONE BY GHRP AND GHRH

The substance P(SP)/bombesin (Bn) antagonists [DArg1DTrp7,9Leu11]SP(P-7482), [DArg1-DPro2DTrp7,9Leu11]SP (P-7483), [DArg1DPhe5DTrp7,9Leu11]SP(P-7492), and the growth hormone releasing hormone (GHRH) antagonist [DArg2Ala8,9,15]GHRH(1-29)(DC21-366) were tested for their in vitro effects on the release of growth hormone (GH) in the presence of GHRH and growth hormone releasing peptide, HisDTrpAlaTrpDPheLysNH2(GHRP). P-7492, P-7483, and P-7482 decreased, dose-dependently, the release of GH by GHRP (IC50=0.2μM, 0.85μM, and 6 μM, respectively). These antagonists had only a 10-15% inhibitory effect on the stimulated GH release of GHRH even at high dosage. DC21-366 decreased the stimulated release of GH by GHRH (IC50=0.16 μM) but not by GHRP. Neither SP nor Bn had GH releasing or inhibitory effects in this system. © 1991 Academic Press, Inc.