AJP - Gastrointestinal and Liver Physiology, Vol 250, Issue 6 806-G813, Copyright © 1986 by American Physiological Society
Inhibition of ATP levels by quinidine in a human colonic epithelial cell line
K. Dharmsathaphorn, P. Huott, C. A. Cartwright, J. A. McRoberts, K. G. Mandel and G. Beuerlein
The influence of quinidine, a putative K+ channel blocker, on Cl- secretion
induced by vasoactive intestinal polypeptide (VIP) was investigated.
Quinidine inhibited Cl- secretion induced by VIP in T84 cell monolayers. A
similar inhibitory effect of quinidine on Cl- secretion was observed in an
isolated human colon. However, in the isolated human colon, which absorbs
Na+ avidly, inhibition of Na+ absorption predominated. In the T84 cell, the
half-maximal inhibition by quinidine occurred at 60 microM, while 300
microM almost completely inhibited the VIP-induced Cl- secretion. Mucosal
addition of quinidine was at least equally effective compared with serosal
addition, suggesting that quinidine acts on the apical membrane or
intracellularly. Quinidine had little or no effect on VIP-stimulated Cl-
efflux in the first 15 min after its addition, suggesting that blockage of
the Cl- exit pathway on the apical membrane is an unlikely mechanism.
Similarly, quinidine did not inhibit the K+-recycling mechanism on the
basolateral membrane in the first 15 min after its addition. The initial
inhibitory action of quinidine corresponded better with its ability to
decrease cellular ATP levels. Our study suggests that the depletion of
cellular ATP levels may explain the initial inhibitory action of quinidine
on electrolyte transport in the intestine, while the late effect is
multifactorial.
