A possible molecular basis for the effect of gastric anti-ulcerogenic drugs

The exact mechanism of action of the anti-ulcerogenic drugs is still under debate. According to the literature, under normal conditions the cAMP:cGMP ratio in the rat gastric mucosa is approximately 8:10. Following prostacyclin administration, this ratio transiently decreases but later shows a strong elevation, indicating profound changes in the intracellular cyclic nucleotide balance. There is evidence that this elevation or 'shift' in the cAMP:cGMP ratio is linked, on a cellular or molecular level, to the anti-ulcerogenic, cytoprotective processes in the stomach. Cimetidine and ranitidine (widely used H2 receptor-blocking drugs) administered at doses that are too low to interfere with gastric acid secretion, cause an elevation in the cAMP:cGMP ratio, an effect that is also observed with other prostaglandin derivatives and anti-ulcerogenic drugs. In this article, Gabor A. Balint discusses these data and how the elevation of the gastric mucosal cAMP:cGMP ratio is a useful molecular marker that could provide insights into the effects of anti-ulcerogenic drugs.