Search

R51619, an agent reported to release endogenous acetylcholine, increased the potential difference and short-circuit current across non-stripped, but not stripped sheets of rat mid-intestine. The response was abolished by both hexamethonium and atropine. R51619 stimulated fluid accumulation by intestinal loops in-vivo suggesting its predominant effect is to stimulate anion secretion. These results are consistent with R51619 releasing endogenous acetylcholine within the myenteric plexus to activate postganglionic cholinergic fibres which stimulate intestinal secretion via muscarinic cholinoreceptors.

Auranofin, applied either mucosally or serosally, increased the potential difference and short-circuit current generated by stripped sheets of rat mid-intestine in a concentration-dependent manner. In-vivo auranofin induced a net fluid secretion, suggesting that the rise in electrical activity represented a stimulation of anion secretion. Removal of chloride or addition of frusemide inhibited the auranofin-induced increase in short-circuit current, indicating that chloride was the anion involved and in the case of serosal auranofin this was confirmed by direct measurement of ion fluxes. The effects of both mucosal and serosal auranofin were calcium-dependent. The gold component of the auranofin molecule is probably responsible for its secretory actions as these were mimicked by chlorauric acid. The ability of auranofin to stimulate intestinal secretion may contribute to its diarrhoeagenic action.

Auranofin in the mucosal fluid caused a dose-dependent inhibition of fluid and Na+ absorption by everted sacs of rat colon. Serosal auranofin was without effect. (Na+ + K+)ATPase activity of homogenates of mucosal scrapes of rat colon was inhibited by auranofin in a dose-related manner, while Mg2+-ATPase activity was little affected. These actions of the drug on colonic transport mechanisms could contribute to the diarrhoea associated with auranofin therapy.

Auranofin in the mucosal fluid inhibited the active Na+-dependent absorption of taurocholic acid by everted sacs of rat ileum. It did not however, affect the passive uptake of taurocholic acid by sacs of mid-intestine. The inhibition by auranofin of active bile acid absorption could result from its previously demonstrated ability to inhibit Na+, K+-ATPase activity. A reduction in the reabsorption of bile acids by the ileum may contribute to the diarrhoea experienced by some patients taking auranofin.