A Weak Substance P Antagonist Inhibits L-692,585-Stimulated GH Release in Swine

Growth hormone (GH) releasing hexapeptide, His-DTrp-Ala-Trp-DPhe- LysNH2 (GHRP-6), was first described as a potent GH-specific secretagogue by Bowers, et al. (2). The first described nonpeptidyl GH secretagogue, L-692,429 (3), has been shown to elicit GH release in many species including swine (4), rats (5), beagles (6), and man (7), while the more potent analogue L-692,585 has also been shown to elicit GH release in beagles (8) and swine (9). L-692,585, a novel nonpeptidyl GH secretagogue analogue of L-692,429, was found to be approximately 20-fold more potent than L-692,429 in rat pituitary cell assays (10) and in beagles in vivo (8). The GH secretagogue activity of L-692,585 has also been reported in swine (9). A weak substance P antagonist, H2N-D-Arg-Pro-Lys-Pro-D-Phe-Gln-D- Trp-Phe-D-Trp-Leu-Leu-NH2 (SPA), has been shown to inhibit GHRP-6 binding in membrane preparations of rat pituitary and hypothalamus (11) and to inhibit both GHRP-6- and L-692,429-stimulated GH responses in rat pituitary cell cultures and in rats in vivo (1). The objective of this study was to determine if SPA could inhibit the GH response elicited by L-692,585 in swine.