[Effect of newly developed analogue of growth hormone releasing peptide [D-Ala-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2 (KP-102)] on growth hormone secretion in adult male rats].

The effect of a newly developed hexapeptide; D-Ala-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2 (KP-102) on GH secretion was studied in adult male rats. KP-102 induced a large plasma GH response at a dose of 0.5 micrograms/kg BW in conscious rats, although GH-releasing abilities of KP-102 varied markedly depending on the phase of GH secretion. Among urethan-anesthetized rats, KP-102 alone exerted a small influence on GH secretion, but it produced a large plasma GH response in the presence of exogenous GH-releasing factor (GRF). The rest of studies were performed on urethan anesthetized rats. During intermittent administration of GRF, the somatotropes became refractory to a large bolus dose of GRF, but KP-102 induced a marked increase of plasma GH. The GH response to KP-102 alone or KP-102 with GRF was significantly augmented when cysteamine HCl was previously administered. Although KP-102 and GRF acted synergistically on GH secretion in control animals, they acted additively in cysteamine-administered rats. Taken together, these findings suggest that the KP-102-induced GH secretion largely depends on GRF and the secretagogue potentiates the GRF effect by antagonizing the SS action at the level of somatotropes. It is concluded that KP-102 alone or in combination with GRF provides a means of stimulating GH secretion in the face of elevated inhibitory tone mediated by SS.