当前位置： SCI文献检索 > BIOCHEMICAL PHARMACOLOGY期刊下所有文献 > Regulation of mastoparan-induced increase of paracellular permeability in T84 cells by RhoA and basolateral potassium channels.

Regulation of mastoparan-induced increase of paracellular permeability in T84 cells by RhoA and basolateral potassium channels.

Abstract：

:Mastoparan, a polypeptide known to activate heterotrimeric GTP-binding proteins, enhances the transport of Ca2+ and K+ across membranes. In the present study we investigated the influence of mastoparan on transepithelial resistance (TER) and on short circuit current (SCC) of the intestinal cell line T84. Mastoparan decreased the TER by 80% of baseline and induced a SCC of 8.34+/-1.38 microAcm(-2). The changes in paracellular conductance were estimated using the nystatin technique and showed that mastoparan increased the paracellular conductance 4-fold. Basolateral Cl(-)-free medium, or blockade of the basolateral Cl(-) uptake via the Na+/K+/2Cl(-) co-transporter with bumetanide, reduced SCC of T84 cells, but did not abolish the effect of mastoparan on the TER. Luminal addition of the Cl(-)-channel blocker DIDS or NPPB had no effect on the increase in SCC. In contrast, blocking the basolateral K(+)-channels by 2mM Ba2+ inhibited both the resistance decrease and elevation of the SCC, and further inhibited the mastoparan-induced increase in intracellular free Ca2. This indicates that mastoparan acts primarily via activating K+ channels with a secondary Cl(-) secretion and Ca2+ influx. Reduction of intracellular free Ca2+ did not alter the effect of mastoparan on TER. Stimulation with mastoparan led to a biphasic rearrangement of actin filaments and increased globular actin content in T84 cells. Depolymerization of actin filaments also correlated with inactivation of Rho-proteins, which are known regulators of the cytoskeleton. Mastoparan induced a 2-fold increase in GDI-complexed Rho. We conclude that mastoparan-induced changes in paracellular permeability are mediated via enhanced basolateral K+ conductance and Rho-protein inactivation. A secondary increase in intracellular Ca2+ or direct interaction of small GTPases with the cytoskeleton are likely mediators of the remodeling of the cytoskeleton with subsequent changes in paracellular permeability.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Blumenstein I,Gerhard R,Ries J,Kottra G,Stein J

doi

10.1016/s0006-2952(03)00043-1

subject

Has Abstract

pub_date

2003-04-01 00:00:00

pages

1151-61

issue

eissn

0006-2952

issn

1873-2968

pii

S0006295203000431

journal_volume

pub_type

杂志文章

在线工具

Regulation of mastoparan-induced increase of paracellular permeability in T84 cells by RhoA and basolateral potassium channels.