Effect of GABA and baclofen on gastric mucosal protective factors.

GABA and baclofen (BAC), a GABA-mimetic agent, were investigated for antiulcerogenic activity. Orally administered GABA (100 mg/kg) and BAC (10 mg/kg) showed significant ulcer protection when given either alone for one day or for 4 days, or when given together with aspirin (ASP; 200 mg/kg x 3 days) in their 4 days treatment time in pylorus-ligated rats. Both the drugs showed a tendency to increase acid and decrease peptic output, and increased gastric mucus secretion in terms of total carbohydrate to protein ratio (TC:P) in both the above treatment groups. ASP tended to decrease acid and increase peptic output and significantly decreased TC:P ratio. Both GABA and BAC tended to reverse aspirin-induced effects, though they had little per se effect on TC:P ratio of gastric mucosal glycoproteins except an increase in sialic acid content both after one day or four days treatment. No, per se, effect on cell shedding (DNA and protein content of gastric juice) or cell proliferation (DNA/mg protein) was noted with GABA or BAC but the enhanced cell shedding induced by ASP was attenuated by them. ASP was found to enhance cell proliferation. However, neither of drug showed any effect on cell proliferation when given either alone or in combination with ASP. The antiulcerogenic effect of GABA and BAC may be due to their predominant effects on mucosal defensive factors like enhanced mucin secretion and decreased cell shedding or mucosal damage.

Effect of continuous infusion of GABA and baclofen on gastric secretion in anaesthetised rats.

Continuous infusion of gamma- aminobutyric acid (GABA) and baclofen (BAC) on gastric acid and pepsin secretion in perfused rat stomach showed that GABA (25-100 mg/kg/hr, i.v.) and BAC (1 mg/kg/hr, i.v.) increased the acid output which was blocked by bicuculline (Bicc, 1 mg/kg, i.v.) when given 30 min before their infusion. However, lower dose of GABA (5 mg/kg/hr) and hig her doses of BAC (5 or 10 mg/kg/hr) did not show any significant effect on acid secretion. GABA (5 and 25 mg/kg/hr) inhibited peptic output and again Bicc in the above dose inhibited the inhibitory effect of 25 mg/kg/hr of GABA on peptic output. The result indicate dichotomy on the effects of GABA on acid and pepsin secretion. As both the effects were blocked by Bicc, involvement of GABAA receptor may be a possibility. The antiulcer effect of GABA and BAC could not be due to their effect on gastric acid secretion, but may be due to inhibition of pepsin secretion by GABA or effects of GABA or BAC on mucosal defensive factors.

Anti-ulcerogenic activity of GABA and GABA mimetic agents in rats.

To elucidate the involvement of peripheral gamma- aminobutyric acid (GABA) and some GABA-mimetic agents in different models of gastric and duodenal ulcerations in rats and guinea pigs, effects of GABA, baclofen (GABAB agonist), diazepam, gamma-butyrolactone (GABA receptor agonist), sodium valproate, isoniazid (GABA-T inhibitor) and glycine (an inhibitory neurotransmitter), given po or ip were studied. All the drugs significantly reduced the ulcer index, incidence and number of ulcer in various models of gastric ulcers except glycine which failed to protect in reserpine-induced ulcers in rats. None of the drugs, except diazepam, had any protective effect on histamine-induced gastric ulcers in guinea pigs. Similarly, no protection was observed by any drug against cysteamine-induced duodenal ulcers in rats, while sodium valproate, isoniazid and glycine significantly decreased number of ulcers against histamine-induced duodenal ulcer in guinea pigs. The results suggest that GABA and GABA-mimetic agents, and glycine, an inhibitory neurotransmitter, afforded protection against some experimental models of peptic ulcer in rats. The effects appear to be due to their inhibitory effect on mucosal defensive factors.

Effect of piracetam, a nootropic agent, on experimental gastric ulcers in rat.

Piracetam, used clinically for cognitive disorders, was found to have significant anti-ulcerogenic activity against immobilization stress- and aspirin-induced gastric ulcers in rats. The anti-ulcer effect of piracetam was exerted by augmentation of mucosal resistance. This was indicated by the significant attenuation of the decrease in total carbohydrate: protein ratio induced by aspirin. It also reversed the marked increase in gastric juice protein and DNA induced by aspirin, indicating that piracetam attenuated the augmented mucosal cell exfoliation induced by the ulcerogen. The drug also increased gastric mucosal serotonin concentrations. Piracetam, thus appears to have a profile of activity associated with cytoprotective agents.