Central GABA-ergic mechanism in stress-induced gastric ulceration.
The effect of exogenous administration of central amino acid neurotransmitters gamma-aminobutyric acid (GABA), glycine, glutamic acid and aspartic acid) into the cerebroventricular system was studied on gastric ulceration induced in albino rats either by 2 h restraint at 4 degrees C or by 6 h restraint at room temperature (30 +/- 2 degrees C). GABA (5, 10, 20 and 50 micrograms) injected intracerebroventricularly (i.c.v.) showed a dose-dependent reduction of gastric ulceration induced by 2 h restraint at 4 degrees C (CRU), whereas glycine (5, 10 and 20 micrograms i.c.v.) failed to alter this response. Muscimol (5 and 10 micrograms i.c.v.), a GABA agonist, and sodium valproate (400 mg kg-1 p.o.), which increases the concentration of GABA in the CNS, significantly reduced CRU. Pretreatment with the GABA antagonists, bicuculline (40 micrograms i.c.v.) or picrotoxin (5 micrograms i.c.v.) reversed the anti-ulcerogenic effects of GABA (50 micrograms i.c.v.) and sodium valproate (400 mg kg-1 p.o.). Bicuculline (20 and 40 micrograms i.c.v.) and picrotoxin (5 and 10 micrograms i.c.v.) per se did not induce gastric ulceration in normal rats but significantly enhanced the minimal ulcerogenic response induced by 6 h restraint at room temperature. Pretreatment with GABA (i.c.v.) significantly reduced the gastric ulceration induced by i.c.v. administration of acetylcholine and adrenaline or pylorus ligation. Glutamic acid (20 micrograms i.c.v.) and aspartic acid (20 micrograms i.c.v.) did not significantly enhance the minimal ulcerogenic response induced by 6 h restraint at room temperature. These observations show that GABA in the CNS exerts an inhibitory effect on stress-induced ulcerogenesis.
Bhargava
K P
KP
Gupta
G P
GP
Gupta
M B
MB
D000109:Acetylcholine / Q000494:pharmacology; D000596:Amino Acids / Q000502:physiology; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D003080:Cold Temperature; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007276:Injections, Intraventricular; D008297:Male; D018377:Neurotransmitter Agents / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D011708:Pylorus / Q000502:physiology; D051381:Rats; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000209:etiology / Q000503:physiopathology*; D013315:Stress, Psychological / Q000150:complications*; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000109:Acetylcholine; D000596:Amino Acids; D001224:Aspartic Acid; D001640:Bicuculline; D004837:Epinephrine; D005971:Glutamates; D018698:Glutamic Acid; D005998:Glycine; D018377:Neurotransmitter Agents; D010852:Picrotoxin; D014635:Valproic Acid; D005680:gamma-Aminobutyric Acid