Inhibitory effect of indomethacin on skin permeability reactions mediated by heat-labile enterotoxins of Salmonella weltevreden, Escherichia coli and Vibrio cholerae.

Indomethacin, a rapid and intense inhibitor of prostaglandin synthesis, was used with a view to find out similarity in secretory mechanism of heat-labile enterotoxins of three diarrhoea producing enteric bacteria viz., Salmonella weltevreden, Escherichia coli and Vibrio cholerae in rabbits. A significant inhibition (90% to 94%) of biological activity of indomethacin pretreated Salmonella enterotoxin was evident in indomethacin treated rabbits, whereas the biological activity was found comparatively low (28% to 76%) in the untreated enterotoxin preparations. In contrast, the skin permeability reaction to cholera toxin remained unaltered in the absence of pretreatment of cholera toxin with indomethacin and it dropped to 55% in pre-treated toxin preparations. There was complete inhibition of biological activity of E. coli enterotoxin which did not receive indomethacin pretreatment. Based on these observations it may be inferred that indomethacin inhibits skin permeability response of heat labile enterotoxin of S. weltevreden both by blocking the effect of prostaglandins (Blocking mechanism) as well as by prostaglandin-adenyl cyclase pathway. The reduction in the biological activity of cholera toxin seems to be occurring through blocking of prostaglandins by indomethacin. In case of E. coli enterotoxin the inhibition mechanism seems operating through prostaglandin-adenyl cyclase system. These observations indicate that the Salmonella enterotoxin shares some similarity with enterotoxins of E. coli and Vibrio cholerae in respect of mechanism of action.