ABSTRACT
Ability of Ala5, Orn9-somatostatin to inhibit the secretion of insulin, glucagon, somatotropic hormone (STH) and prolactin was tested on the model of primary monolayer culture of isolated insular pancreatic and adenohypophyseal cells. Chemical substitution performed between positions 5 and 9 in somatostatin molecule failed to change essentially hormone's biologic activity in suppression of insulin and glucagon in the culture of pancreatic insular cells isolated from newborn rats. Somatostatin analog revealed its natural hormonal ability to inhibit STH secretion but failed to affect that of prolactin. The results are suggestive of the principal possibility to produce somatostatin biologically active analog through lyzine residue substitution in position 9 with obligatory simultaneous substitution amino acid residue in position 5.
Subject(s)
Pancreatic Hormones/antagonists & inhibitors , Pituitary Hormones/antagonists & inhibitors , Somatostatin/analogs & derivatives , Somatostatin/pharmacology , Animals , Cells, Cultured , Male , Pancreatic Hormones/metabolism , Pituitary Hormones/metabolism , Rats , Structure-Activity Relationship , Time FactorsABSTRACT
A total chemical synthesis of [Ala5, Orn9]somatostatin has been performed. This structural analogue of natural somatostatin inhibits the release of somatotropin, insulin and glucagon, but shows no inhibitory effect on secretion of prolactin.
Subject(s)
Somatostatin/analogs & derivatives , Somatostatin/pharmacology , Animals , Cells, Cultured , Chromatography, Thin Layer , Circular Dichroism , Glucagon/metabolism , Growth Hormone/metabolism , Insulin/metabolism , Insulin Secretion , Islets of Langerhans/metabolism , Pituitary Gland, Anterior/metabolism , Prolactin/metabolism , Rats , Somatostatin/chemical synthesisABSTRACT
The effect of synthetic somatostatin on the basal and stimulated secretion of growth hormone and prolactin under conditions of incubation of the adenohypophysis (ADH) tissue in vitro was studied. The labeled growth hormones (GH) and prolactin (Pl) secreted was assayed by the method of electrophoresis in polyacrylamide gel as modified by the authors. Synthetic somatostatin (10 and 100 nM) suppressed the basal and stimulated by 2--0-dibutyril AMP, theophylline, and prostaglandins of E series GH labeled secretion. In doses of 100 nM the inhibitor also suppressed the basal and the stimulated by 2--0-dibutyril AMP and theophylline release of labeled Pl. Apparently, the inhibitory action of somatostatin involves the reduction of the ADH activity of adenylatecyclase.
