Effect of 3-[p-(trans-4-aminomethylcyclohexylcarbonyl)-phenyl] propionic acid hydrochloride on gastric mucosal blood flow.
The effects of 3-[p-(trans-4-aminomethylcyclohexylcarbonyl)phenyl]propionic acid hydrochloride (TEI-5103, TG-51) on gastric mucosal blood flow (GMBF) in rats, rabbits, and dogs were studied by using hydrogen gas clearance, cross-thermocouple, and 51Cr-labelled erythrocyte methods. TEI-5103 (5 mg/kg i.v.) increased GMBF, measured by hydrogen gas clearance method, in anesthetized rats. At 1-10 mg/kg i.v. it also increased GMBF, measured by cross-thermocouple method, in anesthetized rabbits and dogs. The increasing effect of TEI-5103 was more potent than that of cetraxate. By the intragastric route, TEI-5103 (400 mg/kg) increased the GMBF 1 h after the administration in anesthetized and pylorus-ligated rats. Anti-ulcer doses of TEI-5103 prevented the decrease in the GMBF induced by serotonin or indomethacin in anesthetized rats. The drug also prevented the decrease in gastric mucosal blood volume induced by serotonin. The increase in dog femoral arterial blood flow by TEI-5103 (1-10 mg i.a.) was not affected by propranolol, atropine, diphenhydramine, or aminophylline, nor was it attenuated by pretreatment with indomethacin. TEI-5103, like papaverine, inhibited Ca2+-, PGF2 alpha- and norepinephrine-induced contractions of isolated rabbit coeliac artery. The results indicate that TEI-5103 increases GMBF by acting directly on the gastric microcirculation and that this increasing effect may contribute to the anti-ulcer activity of TEI-5103.
Teijin Institute for Bio-Medical Research, Tokyo, Japan.
K
K
Hoshina
N
N
Okada
K
K
Inoue
M
M
Yamamoto
N
N
Saito
T
T
Takeshita
T
T
Naruchi
D000758:Anesthesia; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002860:Chromium Radioisotopes; D004285:Dogs; D005753:Gastric Mucosa / Q000098:blood supply*; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D007441:Intubation, Gastrointestinal; D008297:Male; D010666:Phenylpropionates / Q000494:pharmacology*; D011708:Pylorus / Q000502:physiology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000187:drug effects
D000897:Anti-Ulcer Agents; D002860:Chromium Radioisotopes; D010666:Phenylpropionates; D012701:Serotonin; C045302:TEI 5103; D007213:Indomethacin