Neuroendocrine regulation of expression of apolipoprotein A-IV gene in intestinal epithelial cells

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The present study investigated the role of neural and endocrine factors in the regulation of expression of apolipoprotein A-IV (A-IV) gene in intestinal epithelial cells. Intravenous infusion of ganglionic blocker, cholinergic antagonist, and NOS inhibitor suppressed the expression of A-IV mRNA in rat ileum, suggesting regulation of A-IV gene by cholinergic and NOergic neurons. A-TV mRNA was not affected byβ-adrenergic, dopaminergic, serotonergic, ATRergic antagonists. Since ganglionic blocker did not suppress the increase in A-IV mRNA level by dietary lipid and in adaptive ileum after massive small bowel resection, the upregulation is unlikely to be associated with nerve. In Caco-2 intestinal cells, PYY upregulated the A-IV gene in time-and dose-dependent manner. VIP, bombesin, and substance P also increased the A-IV mRNA, while somatostatin28 suppressed it and, adrenaline, carbachol, glucagon, GRP, NPY, CGRP, GLP, and Met-enkephaline had no effect. These results suggest that expression of A-IV gene in intestinal epithelial cells is regulated by a number of factors associated with gut hormones and neural peptides.