Cysteamine, the most potent ulcerogenic drug known so far, powerfully activates carbonic anhydrase I, II and IV. In vitro and in vivo studies

Cysteamine is known as the most efficient substance in producing experiment al duodenal ulcers reaching 100% after a single dose administration in rats . It is also described the acid hypersecretion and the duodenal mucosa bloo d flow decrease after cysteamine administration. The mechanism of action is still unknown. Starting from our recent studies which show that carbonic a nhydrase (CA)I is involved in vascular changes and CA II and CA IV are invo lved 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 k idneys using the Maren technique. In vivo, 2 groups of rats Gr.1 (N = 31) r eceived a single s.c. dose of cys teamine, 500 mg/kg b.w. and Gr.2 (N = 32) - s.c. isotonic saline solution. We determined CA I, II and IV activity fro m parietal cells and renal CA IV activity. CA activity was determined by th e stopped-flow method, using a rapid kinetic apparatus HI-TECH SF 51 MX. Th e 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 v ivo cysteamine activated gastric mucosa CA I, CA LI and CA IV and did not m odify the activity of the same isozyme from the kidneys. In vivo and in vit ro CA I activation had confirmed our results, and this fact proved the enzy me's involvement in the vasocontrictive process cysteamine-induced. The pow erful activation of gastric CA II and CA IV through the H+ source, could ex plain the HCl excess produced by cysteamine. The absence of cysteamine acti vating effect on renal CA IV proved organ specificity. The results suggeste d the involvement of gastric mucosa CA I, II and IV in the experi mental cy steamine ulcerogenesis.