title: Mechanism of regulation of rabbit intestinal villus cell brush border membrane Na/H exchange by nitric oxide.
abstract: In the mammalian small intestine, coupled NaCl absorption occurs via the dual operation of Na/H and Cl/HCO(3) exchange on the villus cell brush border membrane (BBM). Although constitutive nitric oxide (cNO) has been demonstrated to alter gastrointestinal tract functions, how cNO may specifically alter these two transporters to regulate coupled NaCl absorption is unknown. In villus cells, inhibition of cNO synthase (cNOS) with l-N(G)-nitroarginine methylester (l-NAME) stimulated Na/H exchange whereas Cl/HCO(3) exchange was unaffected. In villus cell BBM vesicles (BBMV) prepared from rabbits treated with l-NAME, Na/H exchange was also stimulated. d-NAME, an inactive analog of l-NAME, and N(6)-(1-imonoethyl)-l-lysine dihydrochloride, a more selective inhibitor of inducible NO synthase, did not affect Na/H exchange. Kinetic studies demonstrated that the mechanism of stimulation is secondary to an increase in the maximal rate of uptake of Na, without an alteration in the affinity of the transporter for Na. Northern blot studies demonstrated an increase in the message for the BBM Na/H exchanger NHE3, and Western blot studies showed that the immunoreactive protein levels of NHE3 was increased when cNOS was inhibited. Thus these results indicate that cNO under nominal physiological states most likely maintains an inhibitory tone on small intestinal coupled NaCl absorption by specifically inhibiting BBM Na/H expression.
authors.affiliation: Section of Digestive Diseases, West Virginia Univ School of Medicine, Morgantown, WV 26506-9161, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Coon
authors.forename: Guohong
authors.initials: G
authors.lastname: Shao
authors.forename: Sheik
authors.initials: S
authors.lastname: Wisel
authors.forename: Raju
authors.initials: R
authors.lastname: Vulaupalli
authors.forename: Uma
authors.initials: U
authors.lastname: Sundaram
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism; D004751:Enteritis / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*
chemical_list: D027963:Chloride-Bicarbonate Antiporters; D004791:Enzyme Inhibitors; C090663:N(6)-(1-iminoethyl)lysine; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D000643:Ammonium Chloride; D009569:Nitric Oxide; D012964:Sodium; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D008239:Lysine; D019331:NG-Nitroarginine Methyl Ester