Gastric anti-ulcerogenic drug effect. A possible mechanism of its molecular basis.

During experimental gastric ulceration in rats an elevation in the mucosal cAMP/cGMP ratio can be encountered. The cause of this significant elevation is mainly (but not entirely) the dramatic fall of the cGMP level. Similar observations were obtained with prostacyclin application (100 micrograms/kg, p.o.), too. This prostaglandin derivative is well known, among others, because of its pronounced anti-ulcerogenic (cytoprotective) effect, too. Other substances of different molecular structure and properties may also exert such effect. The exact mechanism of action of this above-mentioned cytoprotection is still not completely understood. H2-receptor blocker drug cimetidine, given in such small dose (5 mg/kg, p.o.) which does not interfere with gastric acid secretion, also exerts very significant cytoprotective effect in stress (restraint)- and drug (indomethacin)-induced gastric ulcer models. Under cimetidine effect--together with a noticeable endogenous prostacyclin mobilization--the gastric mucosal cAMP/cGMP ratio was also strongly elevated. We conclude that this elevation in the mucosal cAMP/cGMP ratio might be a possible molecular basis of the gastric cytoprotective (anti-ulcerogenic) drugs but it needs further investigations whether all substances exerting cytoprotective effect, e.g. atropine, somatostatin, sulfhydryl drugs, etc., have the same "shifting" property or not? Moreover the phenomenon of the so-called "adaptive cytoprotection" can not be ruled out completely either, therefore this problem needs attention, too.