Oxyntomodulin and related peptides control somatostatin secretion in RIN T3 cells.
We studied the effects of oxyntomodulin (OXM), of its C-terminal (19-37) fragment (OXM (19-37)) and of glucagon (GLU) on somatostatin release, cyclic AMP accumulation and inositol phosphate turnover in somatostatin-secreting RIN T3 cells in culture. Rapid changes in cellular free Ca2+ were also measured using fura-2. Carbachol was used as a control test agent for the parameters involving the inositol phosphate/Ca2+ cascade. OXM, GLU and OXM (19-37) were all able to stimulate somatostatin release with relative ED50 of approx. 1, 22 and 45, respectively. OXM and GLU stimulated cyclic AMP levels with relative ED50 of approx. 1 and 30, respectively, whereas OXM (19-37) was totally ineffective on this parameter. In contrast to carbachol, none of the peptides significantly modified the inositol phosphate turnover or induced rapid changes in cellular free Ca2+. We conclude that the RIN T3 cells contain a receptor-cyclic AMP system similar to that found in gastric mucosa and that this system is linked to somatostatin release. Another receptor-second messenger mechanism linked to somatostatin release is triggered by the (19-37) fragment. This mechanism is not the inositol phosphate/Ca2+ cascade triggered in the same cells by cholinergic agents.
Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
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Tani
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Le Quellec
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Jarrousse
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Sladeczek
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Martinez
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Estival
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Pradayrol
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Bataille
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000494:pharmacology; D004763:Glucagon-Like Peptides / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007340:Insulinoma / Q000378:metabolism*; D053772:Oxyntomodulin; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D012636:Secretory Rate / Q000187:drug effects; D013004:Somatostatin / Q000096:biosynthesis / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007295:Inositol Phosphates; D053772:Oxyntomodulin; D010446:Peptide Fragments; D013004:Somatostatin; D004763:Glucagon-Like Peptides; D002217:Carbachol; D005934:Glucagon; D000242:Cyclic AMP; D002118:Calcium