Somatostatin analogs inhibit somatostatin secretion from cultured hypothalamus cells.
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-AA1,2,4,5,12,13[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.
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology
D011976:Receptors, Muscarinic; D013004:Somatostatin; D002217:Carbachol