Involvement of neuronal processes and nitric oxide in the inhibition by endotoxin of pentagastrin-stimulated gastric acid secretion

Naunyn Schmiedebergs Arch Pharmacol. 1994 May;349(5):523-7. doi: 10.1007/BF00169142.

Abstract

Administration of E. coli endotoxin (1 mg kg-1, i.v.) abolished the acid response induced by the i.v. infusion of pentagastrin (8 micrograms kg-1 h-1) in the continuously perfused stomach of the anaesthetized rat. Local serosal application of tetrodotoxin (36 ng per rat) completely restored acid responses to pentagastrin in endotoxin-treated rats. However, pretreatment with atropine (0.5 mg kg-1, s.c.), capsaicin (20, 30, and 50 mg kg-1, s.c. 2 weeks before the study) or guanethidine (16 mg kg-1, s.c. 3 and 16h before) did not influence the inhibitory effects of endotoxin. Continuous i.v. infusion with NG-nitro arginine methyl ester (L-NAME, 10 mg kg-1 h-1) restored the secretory responses to pentagastrin in endotoxin treated rats. The effects of L-NAME were reversed by L-arginine (100 mg kg-1 h-1, i.v.), but not by its enantiomer D-arginine (100 mg kg-1 h-1, i.v.). The secretory responses elicited by pentagastrin (10(-10)-10(-6) M) in the isolated lumen perfused stomach of the rat were not influenced by incubation (100 min) with endotoxin (10 micrograms ml-1). These observations with tetrodotoxin indicate that inhibition of acid secretion by endotoxin in vivo involves neuronal activity, while inhibition of NO synthesis had a comparable inhibitory action. Activation of a systemic non-adrenergic non-cholinergic neuronal pathway involving NO could thus mediate the acute acid inhibitory effects of endotoxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Drug Interactions
  • Endotoxins / pharmacology*
  • Escherichia coli*
  • Female
  • Gastric Acid / metabolism*
  • Gastric Mucosa / metabolism
  • Infusions, Intravenous
  • Lipopolysaccharides / pharmacology
  • Male
  • NG-Nitroarginine Methyl Ester
  • Neurons / drug effects
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / pharmacology*
  • Pentagastrin / antagonists & inhibitors*
  • Pentagastrin / pharmacology
  • Phenylephrine / pharmacology
  • Rats
  • Rats, Wistar
  • Stomach / drug effects*
  • Tetrodotoxin / pharmacology

Substances

  • Endotoxins
  • Lipopolysaccharides
  • Phenylephrine
  • Nitric Oxide
  • Tetrodotoxin
  • endotoxin, Escherichia coli
  • Arginine
  • Pentagastrin
  • NG-Nitroarginine Methyl Ester