HEAT-STABLE TOXIN FROM ESCHERICHIA-COLI ACTIVATES CHLORIDE CURRENT VIA CGMP-DEPENDENT PROTEIN-KINASE

被引:14
作者
LIN, MQ
MACLEOD, K
GUGGINO, S
机构
[1] JOHNS HOPKINS UNIV, DEPT MED, DIV GASTROENTEROL, BALTIMORE, MD 21205 USA
[2] JOHNS HOPKINS UNIV, DEPT NEUROSCI, BALTIMORE, MD USA
关键词
DIARRHEA; CHANNEL; T84; CELLS; KINASE; INTESTINE;
D O I
10.1159/000154737
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Heat-stable toxin (STa) increases cyclic GMP (cGMP) in isolated intestinal cells and in T84 cells, a colonic secretory cell line. Whole-cell current recordings from patch clamp experiments show identical properties for currents activated by either STa or the cystic fibrosis transmembrane conductance regulator (CFTR) channel. STa-activated currents display a linear current-voltage relationship and a relative permeability sequence of Br > Cl > I. STa or 8-Br-cGMP-activated currents remain when 20 mu M Walsh inhibitor, a blocker of protein kinase A (PKA), is added in the pipette, suggesting that cGMP-dependent protein kinase (PKG) activates the currents. Intracellular addition of Rp-8-Br-cGMP, an agent that activates PKGII and inhibits PKGI and PKA, causes induction of a chloride conductance identical to that stimulated by STa. We conclude that STa activates CFTR by phosphorylation with cGMP-dependent protein kinase.
引用
收藏
页码:23 / 32
页数:10
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