Modulation of intestinal paracellular permeability by intracellular mediators and cytoskeleton.
The influence of cytoskeletal inhibitors (cytochalasin E and colchicine) and intracellular mediators (cAMP, Ca2+, and protein kinase C) in the control of paracellular permeability to mannitol has been examined in rat jejunum in Ussing-type chambers. Cytoskeletal inhibitors, cytochalasin E (20 mumol.L-1) or colchicine (0.5 mmol.L-1), when present in mucosal, serosal, or in both mediums, significantly increase unidirectional mannitol fluxes. Exposure of mucosal and serosal intestinal surface to 10 mmol.L-1 theophylline or 1 mmol.L-1 cyclic AMP analogue for raising the intracellular cAMP enhances paracellular permeability. In Ca(2+)-free physiological medium passive permeability strongly increases. Alterations of cytosolic Ca2+ levels induced by the Ca2+ ionophore A23187 (20 mumol.L-1) or by 0.3 mmol.L-1 TMB-8, a Ca2+ releasing inhibitor from the intracellular stores, enhance mannitol flux. Addition of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate, which activates protein kinase C (PKC), also induces a large increase in the intestinal permeability to mannitol. These results provide evidence that tight junctions and consequently epithelial paracellular permeability can be physiologically controlled by intracellular mediators (Ca2+, cAMP, and PKC) probably through modulation of the cytoskeleton activity.
Pérez
M
M
Departamento de Fisiología y Nutrición, Universidad de Navarra, Pamplona, Spain.
Barber
A
A
Ponz
F
F
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003572:Cytochalasins / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology; D007583:Jejunum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002121:Calcium Channel Blockers; D003572:Cytochalasins; D007476:Ionophores; C007215:cytochalasin E; D000001:Calcimycin; D008353:Mannitol; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D003078:Colchicine; D002118:Calcium