Pirenzepine prevents cysteamine-induced formation of gastroduodenal ulcers and reduction of mesenteric circulation.
The effects of pirenzepine on gastric and duodenal ulceration and barrier mucus levels, as well as on changes of superior mesenteric artery diameter caused by cysteamine, were investigated in rats and compared with those of atropine. Cysteamine induced severe gastric and duodenal ulcers and decreased both barrier mucus levels and mesenteric blood flow. Pirenzepine reduced gastric and duodenal ulceration induced by cysteamine. Moreover, pirenzepine significantly increased basal mesenteric artery diameter and fully prevented cysteamine-induced decrease in mesenteric blood flow. Under the same conditions, atropine failed to prevent gastric and duodenal ulceration or mesenteric artery changes caused by cysteamine. Both pirenzepine and atropine were without any effect on cysteamine-induced inhibition of gastric and duodenal barrier mucus levels. The present results are consistent with the view that pirenzepine protects against gastroduodenal ulceration caused by cysteamine by increasing blood flow at the level of the ulcerated mucosa. The higher affinity of pirenzepine for the muscarinic receptors of sympathetic ganglia may explain the difference between the effects of pirenzepine and atropine. In addition to this, the measurement of superior mesenteric artery diameter changes may represent an accurate and reproducible method, suitable for studying the gastrointestinal protective mechanisms of the drugs.
Bernardini
M C
MC
Institute of Medical Pharmacology, University of Pisa, Italy.
Blandizzi
C
C
Morini
G
G
Chiavarini
M
M
Impicciatore
M
M
Del Tacca
M
M
D000818:Animals; D000897:Anti-Ulcer Agents; D001285:Atropine / Q000494:pharmacology; D001626:Bethanechol Compounds / Q000494:pharmacology; D003543:Cysteamine / Q000633:toxicity*; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000517:prevention & control; D004386:Duodenum / Q000502:physiology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects; D008638:Mesenteric Arteries / Q000033:anatomy & histology / Q000187:drug effects; D010890:Pirenzepine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013152:Splanchnic Circulation / Q000187:drug effects*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control
D000897:Anti-Ulcer Agents; D001626:Bethanechol Compounds; D010890:Pirenzepine; D003543:Cysteamine; D001285:Atropine