1-Naphthylisothiocyanate-induced permeability of hepatic tight junctions to proteins.
We have studied the early action of 1-naphthylisothiocyanate (ANIT) in relation to its effect on the permeability barrier formed by hepatic tight junctions. Materials having different Mr values [inulin (5000), horseradish peroxidase (HRP) (40,000), ovalbumin (also 40,000) and pig gamma-globulin (IgG) (160,000)] were individually pulsed, within 1 min, into perfused rat livers operating under single-pass conditions. In untreated rats, a small peak of HRP and ovalbumin and a comparatively larger peak of inulin were observed in the bile at 7 min. In rats treated with ANIT, with increasing duration of ANIT treatment the inulin peak increased proportionally, whereas the HRP and ovalbumin peaks remained unchanged until after 10 h of ANIT exposure; gamma-globulin was not detected in the 7 min bile sample until after 14 h of ANIT treatment. Bile flow in all rats remained approximately the same until after 14 h of ANIT pretreatment, when substantial bile-flow reduction was observed. Phenobarbitone pretreatment increased the effect of ANIT and massively elevated the first HRP peak; it also shortened the time (to 4 h) at which the increase in permeability to this protein was observed. In contrast, the first HRP peak was virtually abolished in rats that had received the mixed-function-oxidase inhibitor SKF 525A. These experiments suggest that (i) ANIT progressively increased the permeability of the junctional barrier before the reduction in bile flow, (ii) the ANIT-increased permeability change seems to be inversely dependent upon the Mr of the infused proteins, and (iii) metabolites of ANIT were involved in the development of the junctional permeability change.
D015058:1-Naphthylisothiocyanate / Q000494:pharmacology*; D000818:Animals; D001646:Bile / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D006735:Horseradish Peroxidase / Q000378:metabolism; D066298:In Vitro Techniques; D007365:Intercellular Junctions / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013861:Thiocyanates / Q000494:pharmacology*
D011506:Proteins; D013861:Thiocyanates; D015058:1-Naphthylisothiocyanate; D011335:Proadifen; D006735:Horseradish Peroxidase; D010634:Phenobarbital