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16,16‐dimethyl prostaglandin E 2 modulation of endothelial monolayer paracellular barrier function
Author(s) -
Ma Thomas Y.,
Pedram Ali
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199605)167:2<204::aid-jcp3>3.0.co;2-t
Subject(s) - paracellular transport , barrier function , tight junction , endothelial stem cell , microbiology and biotechnology , prostaglandin e2 , forskolin , prostaglandin , adherens junction , endothelium , chemistry , medicine , endocrinology , biology , permeability (electromagnetism) , biochemistry , cell , membrane , cadherin , stimulation , in vitro
Prostaglandins prevent gastrointestinal mucosal injury and promote healing following mucosal injury by various noxious agents. Preservation or repair of microvascular function appears to be crucial in these processes. The processes involved in prostaglandin‐mediated repair and preservation of endothelial function are unclear. In the present study, we investigated the role of prostaglandins on endothelial paracellular barrier function using the filter‐grown bovine aortic endothelial cell monolayers. Endothelial paracellular barrier function was assessed using a paracellular marker, mannitol. Prostaglandin analogs 16,16‐dimethyl prostaglandin E 2 (DMPGE 2 ) and prostaglandin I 2 (PGI 2 ) caused an enhancement of endothelial monolayer paracellular barrier function as evidenced by a dose‐dependent decrease in endothelial paracellular permeability. DMPGE 2 induced enhancement of endothelial paracellular barrier function correlated directly with increasing intracellular cAMP levels. Agents which increase intracellular cAMP levels at different stages of cAMP amplification cascade including phosphodiesterase inhibitor (3‐isobutyl‐1 methylxanthine [IBMX]), membrane permeable cAMP (8‐bromo cAMP), and adenylate cyclase activators (isoproterenol and forskolin) also produced enhancement in endothelial paracellular barrier function. DMPGE 2 enhancement of paracellular barrier function correlated with dense accumulation of actin microfilaments near the intercellular junctions. IBMX, isoproterenol, forskolin, and 8‐bromo cAMP also produced similar changes in endothelial actin microfilaments. Cytochalasin B prevented the DMPGE 2 enhancement of paracellular barrier function. Indomethacin (INDO), a cyclooxygenase inhibitor, caused a dose‐dependent increase in endothelial paracellular permeability. Pharmacologic doses of INDO resulted in condensation and disruption of actin microfilaments with formation of large paracellular openings or gaps between the adjacent cells. Pretreatment of endothelial monolayers with DMPGE 2 prevented INDO‐induced disturbance of actin microfilaments and paracellular barrier function. IBMX, isoproterenol, forskolin, and 8‐bromo cAMP also prevented INDO‐induced changes in actin microfilaments and paracellular barrier function. These findings indicate that DMPGE 2 has a paracellular barrier enhancing effect on filter‐grown endothelial monolayers. This effect appears to be mediated through intracellular cAMP and actin microfilaments. © 1996 Wiley‐Liss, Inc.