Ca2+ and p38 MAP kinase regulate mAChR-mediated c-Fos expression in avian exocrine cells

Muscarinic acetylcholine receptors (mAChRs) in exocrine tissue from the avi an nasal salt gland are coupled to phospholipase C and generate inositol ph osphate and Ca2+ signals upon activation. An early effect of receptor activ ation in the secretory cells is a transient accumulation of c-Fos protein. In cooperation with constitutively expressed Jun, Fos presumably serves as a transcription factor altering gene expression during cell growth and diff erentiation processes in the gland associated with adaptation to osmotic st ress in animals. Nothing is known, however, about the mAChR-dependent signa ling pathways leading to Fos expression in these cells. By incubation of is olated nasal gland tissue in short-term culture with activators or inhibito rs of signaling pathways and quantitative Western blot analysis of Fos abun dance, we have now identified the sustained elevation of the intracellular Ca2+ concentration and the activation of the p38 mitogen-activated protein (MAP) kinase as intermediate signaling elements for the regulation of c-Fos by muscarinic receptor activation. It is suggested that p38 MAP kinase, ra ther than exclusively mediating stress responses, is involved in the regula tion of cellular growth and differentiation controlled by G protein-coupled receptors.