Role of nitric oxide in the central interferon-alpha-induced inhibition of gastric acid secretion in rats

József Czimmer, Ágnes Király, Imre László Szabó, G. Mózsik, G. Sütö

Research output: Contribution to journalArticle

1 Citation (Scopus)

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. ED50 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.

Original languageEnglish
Pages (from-to)11-16
Number of pages6
JournalCurrent Pharmaceutical Design
Volume19
Issue number1
Publication statusPublished - 2013

Fingerprint

Gastric Acid
Interferon-alpha
Nitric Oxide
NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase
Arginine
Stomach
Pylorus
Nitric Oxide Synthase Type II
Ligation
Protein Isoforms
Cytokines
Injections

Keywords

  • Brain-gut interactions
  • Central nervous system
  • cNOS
  • Cytokines
  • iNOS
  • NOS inhibitors
  • Peripheral and central interferon-alpha action
  • Pylorus ligation
  • Vago-vagal reflex

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

Cite this

Role of nitric oxide in the central interferon-alpha-induced inhibition of gastric acid secretion in rats. / Czimmer, József; Király, Ágnes; Szabó, Imre László; Mózsik, G.; Sütö, G.

In: Current Pharmaceutical Design, Vol. 19, No. 1, 2013, p. 11-16.

Research output: Contribution to journalArticle

@article{ce8b1977bc1d4df59f611bf5b0dea33e,
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. ED50 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.",
keywords = "Brain-gut interactions, Central nervous system, cNOS, Cytokines, iNOS, NOS inhibitors, Peripheral and central interferon-alpha action, Pylorus ligation, Vago-vagal reflex",
author = "J{\'o}zsef Czimmer and {\'A}gnes Kir{\'a}ly and Szab{\'o}, {Imre L{\'a}szl{\'o}} and G. M{\'o}zsik and G. S{\"u}t{\"o}",
year = "2013",
language = "English",
volume = "19",
pages = "11--16",
journal = "Current Pharmaceutical Design",
issn = "1381-6128",
publisher = "Bentham Science Publishers B.V.",
number = "1",

}

TY - JOUR

T1 - Role of nitric oxide in the central interferon-alpha-induced inhibition of gastric acid secretion in rats

AU - Czimmer, József

AU - Király, Ágnes

AU - Szabó, Imre László

AU - Mózsik, G.

AU - Sütö, G.

PY - 2013

Y1 - 2013

N2 - 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. ED50 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.

AB - 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. ED50 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.

KW - Brain-gut interactions

KW - Central nervous system

KW - cNOS

KW - Cytokines

KW - iNOS

KW - NOS inhibitors

KW - Peripheral and central interferon-alpha action

KW - Pylorus ligation

KW - Vago-vagal reflex

UR - http://www.scopus.com/inward/record.url?scp=84873974181&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873974181&partnerID=8YFLogxK

M3 - Article

VL - 19

SP - 11

EP - 16

JO - Current Pharmaceutical Design

JF - Current Pharmaceutical Design

SN - 1381-6128

IS - 1

ER -