title: Role of nitric oxide in the central interferon-alpha-induced inhibition of gastric acid secretion in rats.
abstract: Cytokines are known to play a key role in regulation of gastric functions. Interferon-alpha (IFN-α) has been published to impair gastric motility. Aims of this study were to clarify effect of IFN-α on gastric acid secretion (GAS) and determine role of nitric oxide (NO) in the process. Both subcutaneous (1000, 10000, 100 000 IU, s.c.) and intracisternal (10, 100, 1000 IU, i.c.) injections of IFN-α dose-dependently inhibited GAS induced by pylorus ligation in male SD rats in 2 hrs (370±40, 233±39, 208±50 micromol vs control 415±59 micromol and 481±50, 249±75, 141±25 micromol vs control 485±65 micromol, respectively). Central doses inducing same level inhibition were 100 times lower. NOS inhibitor L-NAME (3 mg/kg, i.v.) blocked the inhibitory effect of i.c. ED(50) dose 100 IU IFN-α (507±75 micromol/2 hrs), while L-arginine, the substrate of nitric oxide synthase (NOS) prevented L-NAME action (266±82 micromol/2 hrs). D-arginine failed to prevent L-NAME action on IFN-α-induced inhibition of GAS. Aminoguanidine, a selective inhibitor of inducible NOS (iNOS) failed to block IFN-α induced inhibition of GAS. Results suggest that IFN-α inhibits GAS centrally through nitric oxide pathways probably mediated by continuous isoform of NOS that can be important in regulation of GAS in healthy or pathological conditions.
authors.affiliation: First Department of Medicine, Medical School, University of Pécs, Hungary. jozsef.czimmer@aok.pte.hu
authors.forename: Jozsef
authors.initials: J
authors.lastname: Czimmer
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Király
authors.forename: Imre Laszlo
authors.initials: IL
authors.lastname: Szabó
authors.forename: Gyula
authors.initials: G
authors.lastname: Mózsik
authors.forename: Gabor
authors.initials: G
authors.lastname: Sütő
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002946:Cisterna Magna; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D007267:Injections; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006146:Guanidines; D016898:Interferon-alpha; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester