title: Neurogenic mucosal bicarbonate secretion in guinea pig duodenum.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology and Cell Biology, Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: G
authors.initials: G
authors.lastname: Fei
authors.forename: X
authors.initials: X
authors.lastname: Fang
authors.forename: G D
authors.initials: GD
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: X Y
authors.initials: XY
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Xia
authors.forename: J D
authors.initials: JD
authors.lastname: Wood
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism*; D006168:Guinea Pigs; D006851:Hydrochloric Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009994:Osmolar Concentration; D058912:Purinergic P2Y Receptor Agonists / Q000494:pharmacology; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D058472:Receptors, Purinergic P2Y1 / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D058912:Purinergic P2Y Receptor Agonists; D058921:Purinergic P2Y Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006851:Hydrochloric Acid