Control of c-fos expression in STC-1 cells by peptidomimetic stimuli

Enteroendocrine cells respond to nutrient and non-nutrient stimuli in the g ut lumen. The intestinal hormone cholecystokinin (CCK) is secreted in respo nse to luminal fatty acids, amino acids, peptides and proteins. The peptido mimetic cephalosporins have been reported to provide model, stable, compoun ds with similar secretagogue activity to peptide. Putative luminal stimuli also influence transcriptional activity in enteroendocrine cells, but the m echanisms are uncertain. In the present study we have investigated the cont rol of c-fos expression in STC-1 cells tan enteroendocrine cell line). Pept idomimetics stimulated calcium-dependent release of CCK, and increased intr acellular calcium, phosphorylation of p42/44 mitogen-activated protein kina se (MAP kinase) and c-fos mRNA abundance. Hypotonic stress also increased p 42/44 MAP kinase phosphorylation and c-fos mRNA, but not CCK release. The i ncrease in c-fos mRNA was strikingly potentiated by peptidomimetics in hypo tonic medium. Increased c-Sos expression, but not CCK release, was suppress ed by the MAP kinase (MEK) inhibitor PD98059, and by the tyrosine kinase in hibitor genistein. We conclude that in STC-1 cells, peptidomimetics act thr ough the F42/44 MAP kinase pathway to increase c-fos expression but not exo cytosis. Moreover, a putative non-nutritive stimulus, hypotonic stress, may interact with this pathway to enhance c-fos expression, independently of h ormone release. (C) 2000 Elsevier Science B.V. all rights reserved.