title: Tonic regulation of mouse ileal ion transport by nitric oxide.
abstract: The possible role of nitric oxide (NO) in the regulation of intestinal ion transport was studied in isolated sheets of mouse ileum mounted in Ussing flux chambers. The competitive NO-synthase inhibitors NG-methyl-L-arginine (L-NMA), and NG-nitro-L-arginine (L-NNA) and the effects of NO released from acidified sodium nitrite solution were evaluated in tissues pretreated with guanethidine and atropine. Serosal L-NMA or L-NNA (10-300 microM), but not NG-methyl-D-arginine (D-NMA), produced a sustained concentration-related increase in short-circuit current (Isc) and potential difference (PD) with maximal Isc increases of 50.8 +/- 8.2 and 45.5 +/- 5.8 microAmps/cm2, respectively; mucosal application of L-NMA or L-NNA produced transient increases in Isc. The A50 (and 95% CL) values for serosal L-NMA and L-NNA were 25.6 (15.7-41.9) and 8.7 (5.1-14.9) microM, respectively. L-Arginine (0.1-10 mM), but not D-arginine, produced both a concentration-related reversal of L-NMA or L-NNA-induced increases in Isc. Additionally, pretreatment with L-arginine blocked the L-NMA or L-NNA effects, suggesting a competitive interaction. L-NMA-mediated increases in Isc were unaffected by bicarbonate-free buffer, whereas replacement of chloride ions with gluconate ions almost completely attenuated the response to L-NMA. Further, the effects of L-NMA or L-NNA were blocked by tetrodotoxin or chlorisondamine, suggesting neural actions involving ganglionic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, University of Arizona, College of Medicine, Tucson.
authors.forename: R K
authors.initials: RK
authors.lastname: Rao
authors.forename: P J
authors.initials: PJ
authors.lastname: Riviere
authors.forename: X
authors.initials: X
authors.lastname: Pascaud
authors.forename: J L
authors.initials: JL
authors.lastname: Junien
authors.forename: F
authors.initials: F
authors.lastname: Porreca
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D012977:Sodium Nitrite / Q000494:pharmacology; D019323:omega-N-Methylarginine
chemical_list: D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D012977:Sodium Nitrite