Modification of cation permeability of rabbit descending colon by sulphydryl reagents.

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Abstract
Addition of the organic mercurials mersalyl, p-chloromercuribenzoate [PCMB] and PCMB sulfonate to the Ringer solution (140 mM-Na) bathing the luminal side of isolated epithelia of rabbit descending colon increases short-circuit current (Isc) and tissue conductance (Gt) when the spontaneous Isc is below 2-3 .mu.eq[microequivalents]/cm2 h. The stimulation of Isc by mersalyl is due to an increase in Na absorption, simultaneously K secretion is induced, whereas Cl absorption is not affected. Mersalyl inhibits Isc at Na concentrations < 50 mM. The Na concentration at which Isc is half-maximal (KNa) is shifted by mersalyl from 25 to 133 mM. The overshoot in Isc to a peak value of 5 .mu.eq/cm2 h observed when Na-depleted tissues are suddenly exposed to Na is markedly depressed by mersalyl. Mersalyl inhibits non-competitively the blocking effect of amiloride on Isc. Both the stimulation of Isc and the inhibition of the amiloride effect by mersalyl have the same time course (half-time of the effects 30-40 min) and similar concentration-response curves (half-maximal effects with 2.0-2.6 .times. 10-4 M), indicating a common mechanism. The mersalyl effects on Isc and on the amiloride action are only partially reversed by dimercaptopropanol. PCMB conjugated with dextran (MW 10,000) elicited the same effects as mersalyl. The stoichiometry of the mersalyl-amiloride interaction, estimated by use of the Hill plot, is 1:1; a Hill coefficient of 1 was obtained for the stimulating effect of mersalyl on Isc. One sulfhydryl group/luminal Na entry site controls both Na conductance and cation selectivity. Titration of these sulfhydryl groups by organic mercurials appear to fix the conductance of the luminal Na entry mechanism in a submaximal position and prevent its modulation by amiloride or variations in intra- and/or extracellular Na concentrations.