Direct and indirect actions of HgCl2 and methyl mercury chloride on permeability and chloride secretion across the rat colonic mucosa.
The actions of two mercury compounds, the inorganic HgCl2 and the organic methyl mercury chloride (MeHg), and of CdCl2 on ion transport across the rat colon were studied with the Ussing chamber and the everted sac method. The mercury compounds (5-50 microM), but not CdCl2, administered to the luminal side, induced a large, concentration-dependent increase of tissue conductance (Gt). The transepithelial movement of the extracellular marker, mannitol, was enhanced in the presence of the mercury compounds, indicating that they cause an increase in the permeability of the epithelium. Morphological studies revealed that at least for HgCl2 this increase of the permeability was associated with a loosening of the tight junctions, severe alterations of the enterocytes, and a loss of the continuity of the epithelium. After washing out HgCl2, cells neighboring the altered enterocytes developed lateral processes and in this way restored the continuity of the epithelial layer. In parallel, the mercury compounds induced an increase of short-circuit current (Isc), which is indicative of an induction of Cl- secretion. The increase of Isc, but not that of Gt, was suppressed by indomethacin and, in the case of MeHg, also by tetrodotoxin. These results suggest that MeHg and HgCl2 induce Cl- secretion by an indirect effect on the epithelium, which is mediated by prostaglandins.
Böhme
M
M
Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg/Saar, Germany.
Diener
M
M
Mestres
P
P
Rummel
W
W
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D002712:Chlorides / Q000502:physiology*; D003106:Colon / Q000187:drug effects* / Q000648:ultrastructure; D004848:Epithelium / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D008353:Mannitol / Q000493:pharmacokinetics; D008564:Membrane Potentials / Q000187:drug effects; D008627:Mercuric Chloride / Q000494:pharmacology*; D008767:Methylmercury Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002712:Chlorides; D008767:Methylmercury Compounds; D008353:Mannitol; D008627:Mercuric Chloride