Somatostatin-28 Is Longer Acting and More Selective than Somatostatin-14 on Pituitary and Pancreatic Hormone Release*

Abstract

In the present studies, the large form of somatostatin (SS), SS-28, and an analog [D-Trp²²]SS-28 were reproduced by solid phase synthesis, and the time course of their in vivo biological actions was examined in comparison to that of the tetradecapeptide SS-14. Longitudinal profiles of plasma GH, immunoreactive insulin (IRI), glucagon, and glucose were obtained from freely moving, chronically cannulated rats after the sc administration of 100 μg of SS-28, [D-Trp²²]SS-28, SS-14, or normal saline. Normal saline-treated animals exhibited the typical pulsatile pattern of GH secretion. The administration of SS- 14 resulted in a significant suppression of spontaneous GH surges for only 30 min. In contrast, the administration of SS-28 caused a marked inhibition of spontaneous GH release which persisted for a significantly longer period of time (90 min). At the level of the pancreas, SS-14 inhibited basal IRI release for 45 min. Both SS-28 and [D-Trp²²]SS-28 exhibited potent inhibitory actions on basal IRI release for longer periods of time than did SS-14. Plasma IRI levels remained markedly depressed for 60 min after SS-28 administration, and [D-Trp22]SS-28 significantly prolonged the duration of inhibitory activity of the parent compound to 105 min. In contrast to the effects observed on IRI, the time courses of significant inhibition of plasma glucagon were similar in response to SS-14 and SS-28, although [D-Trp²²]SS-28 prolonged the duration of the inhibitory action of SS-28. Furthermore, marked hyperglycemia was subsequently observed after the administration of SS-28 and [D-Trp²²]SS-28, but not after SS-14 treatment. These results demonstrate that 1) SS-28 is longer acting than SS-14 in inhibiting spontaneous GH and IRI release, 2) D-Trp substitution in position 22 of SS-28 significantly prolongs the duration of inhibition of IRI and glucagon release, and 3) SS-28 compared to SS-14 exhibits selectivity in the time course of action on pancreatic hormone release.