Laboratory Investigation

Kidney International (1982) 21, 44–53; doi:10.1038/ki.1982.7

Effect of protamine on the permeability and structure of rat peritoneum

Nahid Alavi1, Elias Lianos1, Giuseppe Andres1 and Carl J Bentzel1

1Departments of Medicine and Pathology, State University of New York at Buffalo, and Veterans Administration Medical Center, Buffalo, New York, USA

Correspondence: Dr C J Bentzel, Veterans Administration Medical Center, 3495 Bailey Avenue, Buffalo, New York 14215, USA.

Received 10 December 1980; Revised 18 June 1981.

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Abstract

Effect of protamine on the permeability and structure of rat peritoneum. The effect of protamine, a polycationic protein, on the mesothelial permeability and ultrastructure was evaluated in a rat model of peritoneal dialysis. The peritoneal permeability to urea and inulin were measured after the intraperitoneal instillation of protamine sulfate in varying concentrations. A functional correlation was made with the ultrastructure of omentum. Protamine concentrations between 5 and 30 microg/ml decreased the permeability to inulin without significantly altering that of urea. At concentrations from 30 to 75 microg/ml, protamine increased permeability to urea by 50% and to inulin by 20%. Mesothelial cells revealed a loss of microvilli and minor degrees of disorganization of submembranous, cytoplasmic microfilaments without significant changes in the intramembranous structure of occluding junctions. Effects were partially reversible. At a concentration of 100 microg/ml, there was an irreversible doubling in permeability to inulin without a comparable effect on permeability to urea associated with the disruption of occluding junctions in focal areas. This complex response to protamine suggests at least two transperitoneal diffusion pathways, transcellular and paracellular. The mesothelial cell occluding junctions may be a diffusion barrier in the latter pathway.

Effet de la protamine sur la perméabilité et la structure du péritoine de rat. L'effet de la protamine, une protéine polycationique, sur la perméabilité mésothéliale et Fultrastructure a été évalué dans un modèle de dialyse péritonéale du rat. La perméabilité péritonéale à l'urée et à l'inuline a été mesurée après l'instillation intra-péritonéale de sulfate de protamine à diverses concentrations. Des corrélations fonctionnelles ont été faites avec la structure de Iépiploon. Des concentrations de protamine de 5 et 30 microg/ml diminuent la perméabilité à l'inuline sans modifier significativement celle de l'urée. A des concentrations de 30 à 75 microg/ml la protamine augmente la perméabilité à Purée de 50% et à l'inuline de 20%. Les cellules mésothéliales ont perdu leurs microvillosités et il apparaît un certain degré de désorganisation des microfilaments cytoplasmiques sous-membranaires sans modification de la structure intramembraneuse des jonctions. Les effets sont partiellement réversibles. A la concentration de 100 microg/ml il apparait un doublement irréversible de la perméabilité à l'inuline, sans effet comparable sur la perméabilité à l'urée, associée à la rupture focale des jonctions. Cette réponse complexe à la protamine suggère au moins deux voies de diffusion transpéritonéale. transcellulaire et paracellulaire. Les jonctions des cellules mésothéliales peuvent être une barrière de diffusion pour la voie para-cellulaire.

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