Somatostatin Analogs Inhibit Somatostatin Secretion from Cultured Hypothalamus Cells

Abstract

The effect of somatostatin (SRIF) analogs on the secretion of radioimmunoassayable SRIF (SRIF-LI) was studied in the model system of fetal rat hypothalamus cells maintained in long-term, primary dispersed culture. These experiments exploited the biologic activity of certain synthetic SRIFs which cross-react poorly in our standard RIA for SRIF. Carbachol-stimulated SRIF-LI secretion was suppressed by [DTrp⁸]-SRIF-14, [DTrp²²]-SRIF-28 and the octapeptide, des-AA^{1,2,4,5,12,13}[DTrp⁸]-SRIF. Effective concentrations of synthetic analogs were at or below 1 nM. des-Trp⁸-SRIF-14, an analog inactive in all other SRIF biological assays, was similarly ineffective in this assay system at doses up to 10 nM. Following removal of peptide by washing, peptide-treated and control cells responded similarly to depolarization with high potassium buffer. The data demonstrate a direct action of SRIF analogs on the hypothalamus to suppress SRIF-LI release and are consistent with the possibility that an endogenous peptide participates in ‘ultrashortloop’ negative feedback control of its own secretion in the intact animal.