Document Detail

Peripheral GABAB agonists stimulate gastric acid secretion in mice.
MedLine Citation:
PMID:  15210585     Owner:  NLM     Status:  MEDLINE    
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.
Laura Piqueras; Vicente Martinez
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2004-06-21
Journal Detail:
Title:  British journal of pharmacology     Volume:  142     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-07-19     Completed Date:  2005-01-28     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1038-48     Citation Subset:  IM    
Department of Physiology, Pharmacology and Toxicology, Cardenal Herrera CEU University, Valencia, Spain.
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MeSH Terms
Antibodies, Monoclonal / pharmacology
Atropine / pharmacology
Baclofen / analogs & derivatives*,  pharmacology
Deoxyglucose / pharmacology
Dose-Response Relationship, Drug
GABA Agonists / pharmacology*
GABA Antagonists / pharmacology
GABA-A Receptor Agonists
GABA-B Receptor Agonists*
Gastric Acid / secretion*
Gastrins / immunology
Imidazoles / pharmacology
Injections, Intravenous
Mice, Knockout
Muscimol / pharmacology
Organophosphorus Compounds / pharmacology
Pentagastrin / pharmacology
Peptides, Cyclic / pharmacology
Receptors, GABA / drug effects,  physiology
Receptors, GABA-A / physiology
Receptors, GABA-B / physiology
Receptors, Somatostatin / antagonists & inhibitors,  genetics,  physiology
Somatostatin / immunology
Time Factors
gamma-Aminobutyric Acid / pharmacology
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/GABA Agonists; 0/GABA Antagonists; 0/GABA-A Receptor Agonists; 0/GABA-B Receptor Agonists; 0/GABA-C receptor; 0/Gastrins; 0/Imidazoles; 0/Organophosphorus Compounds; 0/PRL 2903; 0/Peptides, Cyclic; 0/Receptors, GABA; 0/Receptors, GABA-A; 0/Receptors, GABA-B; 0/Receptors, Somatostatin; 0/Sstr2 protein, mouse; 1134-47-0/Baclofen; 117354-64-0/2-hydroxysaclofen; 127729-35-5/3-aminopropyl(methyl)phosphinic acid; 154-17-6/Deoxyglucose; 2763-96-4/Muscimol; 51-55-8/Atropine; 51110-01-1/Somatostatin; 5534-95-2/Pentagastrin; 56-12-2/gamma-Aminobutyric Acid; IGZ30Z24EJ/imidazoleacetic acid

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