Effect of 3-[p-(trans-4-aminomethylcyclohexylcarbonyl)phenyl]propionic acid hydrochloride on gastric mucosal barrier.
Effects of 3-[p-(trans-4-aminomethylcyclohexylcarbonyl)phenyl]propionic acid hydrochloride (TEI-5103, TG-51) on mucosal protection, ion permeability, potential difference, glycoprotein content, and bicarbonate secretion as parameters of the mucosal barrier in rats were studied. TEI-5103 (50-400 mg/kg p.o.) prevented the formation of gastric lesions induced by 75% ethanol, 0.6N HCl, and 0.1N HCl + 60% ethanol. Indometacin (10 mg/kg s.c.) given 30 min prior to TEI-5103 dosing slightly attenuated this protective effect. TEI-5103 (20 mg/ml intragastrically) prevented the increase in acid back-diffusion and ion permeability induced by acetylsalicylic acid (ASA, 5 mg/kg intragastrically). It also inhibited the decrease in mucosal potential difference induced by ASA and resultant lesion formation at 1 h after ASA dosing. TEI-5103 (400 mg/kg p.o.) improved the decrease in mucosal high molecular glycoprotein content induced by ASA (100 mg/kg p.o.), whereas it did not change the normal mucosal glycoprotein content. By intra-luminal perfusion of TEI-5103 (10 and 20 mg/ml/min), an increase in CO2 concentration in the perfusate was observed, suggesting heightened bicarbonate secretion. Its effect at 20 mg/ml/min was same as that of prostaglandin E2 (20 micrograms/ml/min). These findings suggest that TEI-5103 has a cytoprotective effect like prostaglandin and promotes the integrity of the mucosal barrier. These effects of TEI-5103 may contribute to its overall anti-ulcer effect.
Hoshina
K
K
Teijin Institute for Bio-Medical Research, Tokyo, Japan.
Yamazaki
N
N
Takeshita
T
T
Naruchi
T
T
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects*; D006023:Glycoproteins / Q000378:metabolism; D006851:Hydrochloric Acid / Q000633:toxicity; D008297:Male; D010666:Phenylpropionates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000897:Anti-Ulcer Agents; D001639:Bicarbonates; D006023:Glycoproteins; D010666:Phenylpropionates; D000431:Ethanol; C045302:TEI 5103; D006851:Hydrochloric Acid