Effect of a new anti-ulcer drug, (3-[p-(trans-4-aminomethylcyclohexylcarbonyl)-phenyl] propionic acid hydrochloride, TEI-5103) on prostaglandin (PG) levels in rat gastric mucosa.
1. Effect of TEI-5103 on the levels of various prostaglandins (PG's) in rat gastric mucosa was studied by HPLC and RIA methods. 2. When administrated in vivo, TEI-5103 significantly increased the level of prostaglandin E2 (PGE2) but only slightly increased that of prostaglandin I2 (PGI2) or thromboxane A2 (TXA2). 3. In the water-immersion stress model, the PGE2 level in control animals was increased immediately after stress and then decreased gradually to the initial level. Indomethacin (5 mg/kg, s.c.) sustained a lower PGE2 level during the experiment, as well as aggravated the lesions. 4. TEI-5103 (400 mg/kg, p.o.) increased the PGE2 level just before stress, and it resulted in the prevention of lesion formation. 5. TEI-5103 inhibited the activity of 15-OH-PG-dehydrogenase from guinea pig lungs, but did not affect the activity of phospholipase A2 from porcine pancreas.
Yamazaki
N
N
Teijin Institute for Bio-medical Research, Tokyo, Japan.
Hoshina
K
K
Takahama
S
S
Suwa
Y
Y
Takeshita
T
T
Naruchi
T
T
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D015232:Dinoprostone; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D008297:Male; D010666:Phenylpropionates / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D000897:Anti-Ulcer Agents; D010666:Phenylpropionates; D011453:Prostaglandins; D011458:Prostaglandins E; C045302:TEI 5103; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone