Chloride secretion induced by mercury and cadmium: action sites and mechanisms.
The actions of two mercury compounds, HgCl2 and methyl mercury chloride (MeHg), and of CdCl2 on the epithelium of the rat colon were studied with the whole-cell patch-clamp technique and the Ussing chamber. MeHg (50 microM) induced an increase of membrane outward current (I(out)) in enterocytes of isolated crypts patched from the basolateral side. This action was inhibited by a Cl- channel blocker and a K+ channel blocker, indicating an increase of both the Cl- and the K+ conductance. In contrast, HgCl2 (50 microM) did not affect I(out), whereas CdCl2 (50 microM) decreased it slightly. In mucosal preparations all three compounds induced a concentration-dependent increase in short-circuit current (Isc) when administered to the serosal, i.e., contraluminal side. Sensitivity to chloride transport blockers and anion replacement experiments revealed that the increase in Isc represented Cl- secretion. In contrast to the actions of luminally applied mercury compounds, the increase of tissue conductance (Gt) was only small. Tetrodotoxin and indomethacin suppressed the effect of the metal compounds on Isc and Gt, while atropine diminished it only partly. This indicates that the secretory action of these heavy metals has not only a direct effect on epithelial cells but is also mediated by prostaglandins and cholinergic and noncholinergic neurons.
Böhme
M
M
Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg/Saar, Germany.
Diener
M
M
Rummel
W
W
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001665:Binding Sites; D002104:Cadmium / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002712:Chlorides / Q000502:physiology*; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004229:Dithiothreitol / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008628:Mercury / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D002712:Chlorides; D013438:Sulfhydryl Compounds; D002104:Cadmium; D016718:Arachidonic Acid; D008628:Mercury; D004229:Dithiothreitol