Gastric acid inhibitory action of a GABA-related compound, 3-amino-3-phenylpropionic acid, in the rat.
The acid inhibitory properties of 3-amino-3-phenylpropionic acid, a structural GABA analogue, were studied in the perfused rat stomach preparation. 3-Amino-3-phenylpropionic acid, 10 and 30 mg/kg i.v., dose dependently suppressed the gastric acid secretion induced by baclofen (2 mg/kg s.c.). This secretagogue action had been shown to be unaffected by either GABAA or GABAB receptor antagonists. The i.v. administration of 3-amino-3-phenylpropionic acid (3 and 10 mg/kg) was also effective to abolish the acid stimulatory effects of muscimol (1 mg/kg i.v.) and 2-deoxy-D-glucose (200 mg/kg i.v.). 3-Amino-3-phenylpropionic acid, even at the high dose (30 mg/kg i.v.) had no influence on the acid output in response to histamine and bethanechol. Furthermore, 3-amino-3-phenylpropionic acid had no significant effect on the acid secretion induced by electrical vagal stimulation. These results indicate that the antisecretory effect of 3-amino-3-phenylpropionic acid is different from those of antimuscarinics, H2-receptor antagonists and vagal blockade. Together, the results suggest that 3-amino-3-phenylpropionic acid might act in the brain to inhibit central regulation mechanisms of gastric acid secretion, probably through GABA mechanisms.
Hara
N
N
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Natsume
Y
Y
Hara
Y
Y
Goto
Y
Y
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001418:Baclofen / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects*; D014630:Vagus Nerve / Q000502:physiology*
D001626:Bethanechol Compounds; D018723:Bethanechol; C064718:3-amino-3-phenylpropionic acid; D009118:Muscimol; D010649:Phenylalanine; D001285:Atropine; D001418:Baclofen