In:
American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 283, No. 5 ( 2002-11-01), p. C1492-C1500
Abstract:
The present studies were undertaken to examine the possible regulation of apical membrane Cl − /OH − exchanger in Caco-2 cells by protein kinase C (PKC). The effect of the phorbol ester phorbol 12-myristate 13-acetate (PMA), an in vitro PKC agonist, on OH − gradient-driven 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS)-sensitive 36 Cl uptake in Caco-2 cells was assessed. The results demonstrated that PMA decreased apical Cl − /OH − exchanger activity via phosphatidylinositol 3-kinase (PI3-kinase)-mediated activation of PKCε. The data consistent with these conclusions are as follows: 1) short-term treatment of cells for 1–2 h with PMA (100 nM) significantly decreased Cl − /OH − exchange activity compared with control (4α-PMA); 2) pretreatment of cells with specific PKC inhibitors chelerythrine chloride, calphostin C, and GF-109203X completely blocked the inhibition of Cl − /OH − exchange activity by PMA; 3) specific inhibitors for PKCε (Ro-318220) but not PKCα (Go-6976) significantly blocked the PMA-mediated inhibition; 4) specific PI3-kinase inhibitors wortmannin and LY-294002 significantly attenuated the inhibitory effect of PMA; and 5) PI3-kinase activators IRS-1 peptide and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P 3 ] mimicked the effects of PMA. These findings provide the first evidence for PKCε-mediated inhibition of Cl − /OH − exchange activity in Caco-2 cells and indicate the involvement of the PI3-kinase-mediated pathways in the regulation of Cl − absorption in intestinal epithelial cells.
Type of Medium:
Online Resource
ISSN:
0363-6143
,
1522-1563
DOI:
10.1152/ajpcell.00473.2001
Language:
English
Publisher:
American Physiological Society
Publication Date:
2002
detail.hit.zdb_id:
1477334-X
SSG:
12
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