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The lacrimal gland (LG) is an exocrine gland important for secretion of the tear film. The kinase p38 has important signal transduction functions, e.g. in gene transcription, but has previously not been known to modulate exocrine secretion. The aim of the current study was to investigate the role of p38 in carbachol (Cch)-induced LG secretion in LG acinar cells in vitro. Western blotting was used to determine the phosphorylation status of p38 and p42/44 and determine expression of p38 isoforms. To determine the effect of p38 inhibition on LG secretion, PD 169316, a general p38 inhibitor, and SB 239063, an inhibitor of p38α and β, were added to the cells prior to secretion measurements. The results revealed activation of p38 mediated by Cch stimulation and inhibition of Cch-induced secretion as a result of p38 inhibition. The inhibition was observed with PD 169316 isoforms, but not with SB 239063. The p38δ isoform was shown to have robust expression both by Western blotting of acinar cells and immunofluorescence of the whole gland. In conclusion, p38 activation mediates secretion in cholinergic stimulation of rabbit LG cells.
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Role of feed-regulating peptides on pancreatic exocrine secretion

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In recent two decades a group of feed intake-regulating peptides (i.e., leptin, apelin, ghrelin, obestatin and orexins) have been discovered. Besides the central nervous system these regulatory peptides are produced and released by the gastrointestinal (GI) endocrine cells and neurons, and functional receptors were found in the GI tract and the pancreas. High expression of feed intake-regulating peptides was found in the stomach; however, they may be expressed in other GI tissues too. The peptides control gastrointestinal functions, modulate orexigenic drive and energy metabolism via different mechanisms. Basal leptin, apelin, ghrelin and obestatin plasma concentrations correlated with BMI, and we observed significant reduction of ghrelin and leptin concentrations following fundectomy in rats. We have shown previously that exogenous leptin and ghrelin (a peptide derived from the same preprohormone as obestatin) inhibit the secretion of rat pancreatic juice through a neurohormonal mechanism. Intravenous obestatin was found to stimulate pancreatic protein output in anaesthetized rat via a CCK-vagal-dependent mechanism, whilst a direct action of obestatin on rat pancreatic acini in vitro resulted in opposite effect. Intravenous boluses of apelin reduced the juice volume, protein and trypsin outputs in a dose-dependent manner. However, apelin administered into the duodenal lumen significantly increased pancreatic protein and trypsin outputs through a vagal mechanism. Orexin A and B were found to stimulate insulin release, though on the rat exocrine pancreas orexin A had no effect, and the effect of orexin B was weak. Concluding, feed intake-regulating peptides participate in controlling the exocrine pancreas.
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