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THE RELATIONSHIP BETWEEN CYSTEAMINE AND PARIETAL CELL CARBONIC ANHYDRASE IN THE MECHANISM OF EXPERIMENTAL ULCERS

Medicines


THE RELATIONSHIP BETWEEN CYSTEAMINE AND PARIETAL CELL CARBONIC ANHYDRASE IN THE MECHANISM OF EXPERIMENTAL ULCERS

Cysteamine (Cyst) is known as the most efficient substance in producing experimental duodenal ulcers reaching a 100% after a singl 151e49b e dose administration in rats. It is also described the acid hypersecretion and the duodenal mucosa blood flow decrease after Cyst administration. The mechanism of action is still unknown.



AIM: Starting from our recent studies which show that carbonic anhydrase (CA) I is involved in vascular modifications and CA II and CA IV are involved in the secretory modifications we followed the effect of Cyst on these CA isozymes.

MATERIAL AND METHOD: In vitro, we followed the effect of Cyst on CA I, CA II and CA IV isolated from the gastric mucosa patietal cells and from kidneys using the Maren technique (1993). In vivo, 2 groups of rats Gr.1(N=31) received a single s.c. dose of Cyst, 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 (England).

RESULTS:

CA I

CA II

Gastric CA IV

Renal CA IV

In vitro Cyst 10-4M

In vivo Gr.1

In vivo Gr.2

DISCUSSION AND CONCLUSIONS: in vivo and in vitro CA I activation has confirmed our results, and this fact proves the enzyme involvement in the vasocontrictive process produced by Cyst. This substance is well-known as an antagonist of NO vasodilating effects. The powerful activation of gastric CA II and CA IV through the H+ source, could explain the HCl excces produced by Cyst. The absence of Cyst activating effect on renal CA IV proves an organ specificity. The results suggest the involvement of gastric mucosa CA I, II and IV in the experimental Cyst ulcerogenesis.


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