Exacerbation of indomethacin-induced gastric ulceration by systemically administered GABA in rats: possible involvement of peripheral GABA receptors.
Effects of systemically administered gamma-aminobutyric acid (GABA) on indomethacin-induced gastric ulceration were studied in rats. Orally administered GABA significantly exacerbated the ulceration in a dose-dependent manner, although GABA per se had no ulcerogenic activity. The exacerbation was restored by GABA receptor antagonists, bicuculline methiodide, picrotoxin and pentylenetetrazol. Pretreatment with atropine sulfate antagonized the exacerbating effect of GABA on indomethacin-induced ulceration. 3-Amino-1-propanesulfonic acid, but not glycine, taurine or beta-alanine, mimicked the effect of GABA on the ulceration, which was inhibited by picrotoxin. Muscimol and (-)-baclofen could not potentiate the ulceration. However, sodium pentobarbital and diazepam caused synergistic exacerbation of the ulcer when combined with GABA. Since it is known that systemically administered GABA can not penetrate into the brain, these results suggest that systemically administered GABA may stimulate the cholinergic transmission mediating the activation of peripheral GABA receptors, resulting in the exacerbation of indomethacin-induced ulceration.
Hara
S
S
Pharmacological Research Laboratory, Sato Pharmaceutical Co., Ltd., Tokyo, Japan.
Yanagihara
S
S
Satoh
K
K
Morioka
S
S
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004357:Drug Synergism; D005998:Glycine / Q000494:pharmacology; D007213:Indomethacin / Q000633:toxicity*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013276:Stomach Ulcer / Q000139:chemically induced*; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology; D015091:beta-Alanine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology*
D000927:Anticonvulsants; D001285:Atropine; D001640:Bicuculline; D005998:Glycine; D007213:Indomethacin; D009118:Muscimol; D010424:Pentobarbital; D010433:Pentylenetetrazole; D010852:Picrotoxin; D011963:Receptors, GABA-A; D013654:Taurine; D015091:beta-Alanine; D005680:gamma-Aminobutyric Acid; C001355:tramiprosate