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  • Title: Neurogenic mucosal bicarbonate secretion in guinea pig duodenum.
    Author: Fei G, Fang X, Wang GD, Liu S, Wang XY, Xia Y, Wood JD.
    Journal: Br J Pharmacol; 2013 Feb; 168(4):880-90. PubMed ID: 22994306.
    Abstract:
    BACKGROUND AND PURPOSE: To test a hypothesis that: (i) duodenal pH and osmolarity are individually controlled at constant set points by negative feedback control centred in the enteric nervous system (ENS); (ii) the purinergic P2Y(1) receptor subtype is expressed by non-cholinergic secretomotor/vasodilator neurons, which represent the final common excitatory pathway from the ENS to the bicarbonate secretory glands. EXPERIMENTAL APPROACH: Ussing chamber and pH-stat methods investigated involvement of the P2Y(1) receptor in neurogenic stimulation of mucosal bicarbonate (HCO(3)(-)) secretion in guinea pig duodenum. KEY RESULTS: ATP increased HCO(3)(-) secretion with an EC(50) of 160 nM. MRS2179, a selective P2Y(1) purinergic receptor antagonist, suppressed ATP-evoked HCO(3)(-) secretion by 47% and Cl(-) secretion by 63%. Enteric neuronal blockade by tetrodotoxin or exposure to a selective vasoactive intestinal peptide (VIP, VPAC(1)) receptor antagonist suppressed ATP-evoked HCO(3)(-) secretion by 61 and 41%, respectively, and Cl- by 97 and 70% respectively. Pretreatment with the muscarinic antagonist, scopolamine did not alter ATP-evoked HCO3(-) or Cl(-) secretion. CONCLUSION AND IMPLICATIONS: Whereas acid directly stimulates the mucosa to release ATP and stimulate HCO(3)(-) secretion in a cytoprotective manner, neurogenically evoked HCO(3)(-) secretion accounts for feedback control of optimal luminal pH for digestion. ATP stimulates duodenal HCO(3)(-) secretion through an excitatory action at purinergic P2Y(1) receptors on neurons in the submucosal division of the ENS. Stimulation of the VIPergic non-cholinergic secretomotor/vasodilator neurons, which are one of three classes of secretomotor neurons, accounts for most, if not all, of the neurogenic secretory response evoked by ATP.
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