Effects of MCI-727, a new anti-ulcer agent, on plasma secretin concentration in rats and dogs and pancreatic exocrine secretion in rats.
In the present study, we investigated the effects of MCI-727, a new anti-ulcer agent, on plasma immunoreactive secretin concentration in rats and dogs using secretin specific RIA with the ethanol extraction method. Plasma secretin levels were increased dose-dependently 10 min after oral administration of MCI-727 in rats (control: 5.5 +/- 0.6; MCI-727, 10 mg/kg: 10.4 +/- 2.6; 30 mg/kg: 15.3 +/- 1.5; 100 mg/kg: 20.7 +/- 2.6 pg/ml, n = 6). Teprenone also caused a significant increase of plasma secretin at 10 min after oral administration at the doses of 30, 100 and 300 mg/kg. Under the same conditions, MCI-727 and teprenone did not alter the plasma immunoreactive gastrin concentration in rats. From the results of the time course study, the increasing effect of MCI-727 (30 mg/kg, p.o.) on plasma secretin remained for at least 240 min after administration. On the other hand, the increasing effect of teprenone (200 mg/kg, p.o.) was only observed at 30 and 60 min after administration. Furthermore, MCI-727 had increasing effects on plasma secretin concentration in dogs, but teprenone had no effects in this species. The volume of pancreatic secretion and the pancreatic bicarbonate output increased after intra-duodenal administration of MCI-727 at 30 and 100 mg/kg in rats. Similar effects were also observed with teprenone (30-300 mg/kg, i.d.) or secretin (Secrepan, 0.1-1.0 unit/kg, i.v.).
Kawamura
M
M
Pharmaceuticals Laboratory, Mitsubishi Kasei Corporation, Yokohama, Japan.
Yamazaki
S
S
Tobe
A
A
Watanabe
S
S
Takeuchi
T
T
D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005755:Gastrins / Q000097:blood; D007275:Injections, Intravenous; D008297:Male; D010091:Oximes / Q000008:administration & dosage / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D012633:Secretin / Q000097:blood*
D000897:Anti-Ulcer Agents; D001639:Bicarbonates; D004224:Diterpenes; D005755:Gastrins; D010091:Oximes; D010879:Piperazines; C070706:MCI 727; D012633:Secretin; C031049:geranylgeranylacetone