Involvement of neuronal processes and nitric oxide in the inhibition by endotoxin of pentagastrin-stimulated gastric acid secretion.
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.
Martinez-Cuesta
M A
MA
Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain.
Barrachina
M D
MD
Whittle
B J
BJ
Pique
J M
JM
Esplugues
J V
JV
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D007262:Infusions, Intravenous; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009474:Neurons / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010418:Pentagastrin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
D004731:Endotoxins; D008070:Lipopolysaccharides; D010656:Phenylephrine; D009569:Nitric Oxide; D013779:Tetrodotoxin; C044101:endotoxin, Escherichia coli; D001120:Arginine; D010418:Pentagastrin; D019331:NG-Nitroarginine Methyl Ester