Neurogenic mucosal bicarbonate secretion in guinea pig duodenum

Autor:	G-D Wang, XY Wang, Jackie D. Wood, Sumei Liu, X Fang, G Fei, Y Xia
Rok vydání:	2013
Předmět:	Pharmacology medicine.medical_specialty medicine.drug_class Purinergic receptor Vasoactive intestinal peptide Secretomotor Biology Receptor antagonist Endocrinology Purinergic P2Y Receptor Agonists Internal medicine medicine Enteric nervous system Secretion Purinergic P2Y Receptor Antagonists
Zdroj:	British Journal of Pharmacology. 168:880-890
ISSN:	0007-1188
DOI:	10.1111/j.1476-5381.2012.02218.x
Popis:	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 P2Y1 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 P2Y1 receptor in neurogenic stimulation of mucosal bicarbonate (HCO3−) secretion in guinea pig duodenum. Key Results ATP increased HCO3− secretion with an EC50 of 160 nM. MRS2179, a selective P2Y1 purinergic receptor antagonist, suppressed ATP-evoked HCO3− secretion by 47% and Cl− secretion by 63%. Enteric neuronal blockade by tetrodotoxin or exposure to a selective vasoactive intestinal peptide (VIP, VPAC1) receptor antagonist suppressed ATP-evoked HCO3− 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 HCO3− secretion in a cytoprotective manner, neurogenically evoked HCO3− secretion accounts for feedback control of optimal luminal pH for digestion. ATP stimulates duodenal HCO3− secretion through an excitatory action at purinergic P2Y1 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::a25113ddf98cdc84e1c4c94c32bbfc94 https://doi.org/10.1111/j.1476-5381.2012.02218.x Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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