Affordable Access

Publisher Website

Cysteamine, the most potent ulcerogenk drug known so far, powerfully activates carbonic anhydrase I, II and IV.In vitroandin vivostudies

Authors
Journal
Experimental and Toxicologic Pathology
0940-2993
Publisher
Elsevier
Publication Date
Identifiers
DOI: 10.1016/s0940-2993(00)80076-7
Keywords
  • Cysteamine
  • Carbonic Anhydrase I
  • Ii
  • Iv
  • Ulcerogenic Drug
Disciplines
  • Biology

Abstract

Summary Cysteamine is known as the most efficient substance in producing experimental duodenal ulcers reaching 100% after a single dose administration in rats. It is also described the acid hypersecretion and the duodenal mucosa blood flow decrease after cysteamine administration. The mechanism of action is still unknown. Starting from our recent studies which show that carbonic anhydrase (CA) I is involved in vascular changes and CA II and CA IV are involved in the secretory modifications we followed the effect of cysteamine on these CA isozymes. In vitro, we followed the effect of cysteamine on CA I, CA II and CA IV isolated from the gastric mucosa parietal cells and from kidneys using the Mann technique. In vivo, 2 groups of rats Gr.1 (N = 31) received a single s.c. dose of cysteamine, 500 mg/kg b.w. and Gr.2 (N = 32) — s.c. isotonic saline solution. We determined CA I, II and IV activity from parietal cells and renal CA IV activity. CA activity was determined by the stopped-flow method, using a rapid kinetic apparatus HI-TECH SF 51 MX. The results show that in vitro cysteamine activated the purified CA I and CA II, as well as gastric mucosa parietal cell CA IV by a direct mechanism of action. The renal CA IV was not significantly activated by cysteamine. In vivo cysteamine activated gastric mucosa CA I, CA II and CA IV and did not modify the activity of the same isozyme from the kidneys. In vivo and in vitro CA I activation had confirmed our results, and this fact proved the enzyme's involvement in the vasocontrictive process cysteamine-induced. The powerful activation of gastric CA II and CA IV through the H + source, could explain the HCl excess produced by cysteamine. The absence of cysteamine activating effect on renal CA IV proved organ specificity. The results suggested the involvement of gastric mucosa CA I, II and IV in the experimental cysteamine ulcerogenesis.

There are no comments yet on this publication. Be the first to share your thoughts.