Peritoneal permeability in the rat: Modulation by microfilament-active agents

Peritoneal permeability in the rat: Modulation by microfilament-active agents. A model of peritoneal dialysis in the rat was used to determine the effects of cytochalasins on ultrastructure and peritoneal permeability to molecules of varying molecular weight. The permeability to urea, inulin, and plasma albumin were determined after intraperitoneal administration of cytochalasin B (2 to 10 × 10 -6 M) and cytochalasins D and E (2 × 10 -6 M). Cytochalasin B (20 × 10 -6 M) increased the permeability to inulin, urea, and albumin by 30, 60, and 150%, respectively. These effects were, to a large degree, reversible. Cytochalasins D and E produced greater increments in permeability for all molecules; this increase was only partially reversible. Ultrastructure analysis by scanning electron microscopy revealed extensive development of membrane protuberances (zeiotic knobs) on mesothelial cells exposed to cytochalasin B. A return to a normal apical cell surface was apparent although incomplete at 24 hr. Tight junctions were not grossly altered and major changes in intramembranous junctional strands were not observed. The major effect of cytochalasins on the cell surface may be responsible for the increased permeability to urea, predominately a transcellular probe. Inulin, which follows a paracellular route, was less affected. Altered protein permeability may be due to the action of cytochalasin on the exposed capillary endothelium in subdiaphragmatic areas where the mesothelium is discontinuous. Permeabilite peritoneale chez le rat: modulation par des agents actifs sur les microfilaments. Un modele de dialyse peritoneale chez le rat a ete utilise pour determiner les effets de cytochalasines sur l'ultrastructure et la permeabilite peritoneale a des molecules de divers poids moleculaires. La permeabilite a l'uree, a l'inuline, et a l'albumine plasmatique a ete determinee apres administration intraperitoneale de cytochalasine B (2 a 20 × 10 -6 M) et cytochalasines D et E (2 × 10 -6 M). La cytochalasine B (20 × 10 -6 M) a augmente la permeabilite a l'inuline, l'uree, et l'albumine de 30, 60, et 150%, respectivement. Ces effets etaient, pour une large part, reversibles. Les cytochalasines D et E ont entraine des elevations superieures de permeabilite a toutes les molecules; cette augmentation etait seulement partiellement reversible. Une analyse de l'ultrastructure par microscope electronique a balayage a revele le developpement extensif de protuberances membranaires (boutons zeiotiques) sur les cellules mesotheliales exposees a la cytochalasine B. Un retour a une surface cellulaire apicale normale etait apparent, mais incomplet, a 24 hr. Les jonctions serrees n'etaient pas tres alterees, et on n'observait pas de changement important des zones jonctionnelles intramembranaires. Cet important effet des cytochalasines sur la surface cellulaire pourrait etre responsable de l'augmentation de permeabilite a l'uree, un marqueur a predominance transcellulaire. L'inuline, qui suit une voie paracellulaire, etait moins affectee. L'alteration de la permeabilite aux proteines pourrait etre due a l'action de la cytochalasine sur l'endothelium capillaire expose dans les zones sous-diaphragmatiques, ou le mesothelium est discontinu.