Reduction of rat gastric transmucosal potential difference by indomethacin partly associated with its acid secretory activity.

Gastric transmucosal potential difference (PD) is referred to as an index of function and integrity of the mucosa. Gastric instillment of indomethacin for 30 min significantly reduces the PD (lumen negative to serosa) at the glandular portion of the rat stomach, but not at the forestomach. The PD reduction of the glandular portion disappeared by pretreatment with prostaglandin E2 (PGE2), although PGE2 alone produced an increase in PD. The PD decrease induced by indomethacin was greatly recovered by additional treatment with timoprazole, a H+,K+-ATPase inhibitor. Timoprazole alone did not influence gastric PD. These data suggest that indomethacin acutely reduces gastric PD in part through the acid secretory activity, apart from the damaging activity on the mucosa.