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British journal of pharmacology

Peripheral GABAB agonists stimulate gastric acid secretion in mice.


PMID 15210585

Abstract

1 We characterized the effects of intravenous GABA and preferential GABAA (muscimol), GABAB (R-baclofen and SKF-97541) and GABAC agonists (imidazole-4-acetic acid) on gastric acid secretion in urethane-anesthetized mice implanted with a gastric cannula, and determined the role of vagal cholinergic mechanisms, and gastrin and somatostatin by using peptide immunoneutralization, the SSTR2 antagonist, PRL-2903, and SSTR2 knockout mice. 2 The selective GABA(B) agonists R-baclofen (0.1-3 mg kg(-1), i.v.) and SKF-97541 (0.01-0.3 mg kg(-1), i.v.) induced a dose-related stimulation of gastric acid secretion. SKF-97541 was about 10 times more potent than R-baclofen stimulating gastric acid secretion. Neither GABA (0.1-100 mg kg(-1), i.v.) nor muscimol (0.1-3 mg kg(-1)) nor imidazole-4-acetic acid (0.1-10 mg kg(-1)) affected basal gastric acid secretion. 3 Stimulatory effects of SKF-97541 (0.1 mg kg(-1), i.v.) were blocked by the selective GABAB antagonist, 2-hydroxysaclofen, cholinergic blockade with atropine, subdiaphragmatic vagotomy or gastrin immunoneutralization. 4 Somatostatin immunoneutralization or SSTR2 blockade with PRL-2903 enhanced the secretory response to SKF-97541 (0.1 mg kg(-1), i.v.) by 78 and 105%, respectively. 5 In SSTR2 knockout mice, SKF-97541 (0.1 mg kg(-1), i.v.) increased basal gastric acid secretion by 48%. Neither GABA nor muscimol nor imidazole-4-acetic acid modified basal gastric acid secretion in SSTR2 knockout mice. 6 These results indicate that, in mice, stimulation of GABAB receptors increases gastric acid secretion through vagal- and gastrin-dependent mechanisms. Somatostatin implication might be secondary to the release of gastrin and the increase in gastric luminal acidity.

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