US EPA

4971243 

Journal Article 

Chloride Secretion Induced by Mercury and Cadmium: Action Sites and Mechanisms 

Bohme, M; Diener, M; Rummel, W 

1992 

1 

Toxicology and Applied Pharmacology
ISSN: 0041-008X
EISSN: 1096-0333 

114 

2 

Chloride secretion induced by mercury (7439976) and cadmium (7440439) in the rat colon was studied in-vitro. Isolated intact crypts were prepared from the epithelium of the descending colon of female Wistar-rats and mounted on Ussing chambers. Methylmercury-chloride (115093) (MMC), mercuric-chloride (7487947), or cadmium-chloride (10108642) at concentrations of 0 to 50 micromolar (microM) were added to the preparations. In some experiments, 5-nitro-2-(3-phenylpropylamine)benzoate (NPPB), a chloride channel blocker, or barium-chloride (10361372), a potassium (K+) channel blocker was added. The effects on membrane outer current (Iout) and membrane potential were determined using a patch clamp technique. MMC caused a significant increase in Iout as well as significant depolarization in half of the cells and a hyperpolarization in the other half. NPPB and barium-chloride partially inhibited induced Iout increases. Cadmium slightly decreased Iout but had no effect on membrane potential; mercuric-chloride affected neither Iout nor membrane potential. Portions of the mucosal/submucosal epithelium of the descending colon from female Wistar-rats were treated with 0 to 50microM MMC, mercuric-chloride, or cadmium-chloride on the serosal or luminal side. In some experiments, furosemide, indomethacin, quinacrine, atropin, or tetrodotoxin were present. Effects on the short circuit current (Isc) and tissue conductance (Gt) were determined. MMC, mercuric-chloride, and cadmium-chloride caused significant dose related increases in Isc when applied serosally; only MMC and mercuric-chloride caused increases when applied luminally. MMC and mercuric-chloride induced small increases in Gt. Furosemide, indomethacin, and quinacrine significantly decreased induced Isc increases. Tetrodotoxin suppressed the effects of MMC and mercuric-chloride on Isc. Atropine partially inhibited the increase in Isc and blocked the increase in Gt induced by MMC and mercuric-chloride. The authors conclude that heavy metal compounds induce chloride secretion in the rat colon by activation or formation of prostaglandins which subsequently stimulate secretomotor enteric neurons.