Local regulatory mechanisms of gastroduodenal bicarbonate secretion :

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We demonstrated in the present study that 1) endogenous PGs and gas mediators such as NO, H_2S and CO, are involved in the local regulatory mechanism of the acid-induced duodenal HCO_3^- secretion, 2) NO and CO stimulate HCO_3^- secretion at least partly by increasing PG production, 3) the stimulatory action of H_2S is partly mediated by PG and NO as well as by capsaicin-sensitive afferent neurons, 4) PGE_2 stimulates HCO_3^- secretion via activation of EP3/EP4 receptors, and 5) both PDE1 and PDE3 are involved in the regulation of duodenal HCO_3^- secretion. In addition, we also found, using muscarinic (M) receptor knockout mice, that 6) the cholinergic stimulation of duodenal HCO_3^- secretion is mainly mediated by the activation of M1 and M3 receptors and modified by M4 receptors and that 7) the activation of M4 receptors inhibits the release of somatostatin from D cells and results in enhancement of the HCO_3^- response by removing the negative effect of somatostatin.