LONG-TERM UNCOUPLING OF CHLORIDE SECRETION FROM INTRACELLULAR CALCIUM LEVELS BY INS(3,4,5,6)P-4

被引:168
作者
VAJANAPHANICH, M
SCHULTZ, C
RUDOLF, MT
WASSERMAN, M
ENYEDI, P
CRAXTON, A
SHEARS, SB
TSIEN, RY
BARRETT, KE
TRAYNORKAPLAN, A
机构
[1] UNIV CALIF SAN DIEGO,SCH MED,DEPT MED 8414,LA JOLLA,CA 92093
[2] UNIV CALIF SAN DIEGO,SCH MED,DEPT PHARMACOL,LA JOLLA,CA 92093
[3] UNIV CALIF SAN DIEGO,SCH MED,HOWARD HUGHES MED INST,LA JOLLA,CA 92093
[4] UNIV BREMEN,INST ORGAN CHEM,W-2800 BREMEN,GERMANY
[5] NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709
关键词
D O I
10.1038/371711a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
OSMOREGULATION, inhibitory neurotransmission and pH balance depend on chloride ion (Cl-) flux. In intestinal epithelial cells, apical Cl- channels control salt and fluid secretion and are, in turn, regulated by agonists acting through cyclic nucleotides and internal calcium ion concentration ([Ca2+](i))(1-3). Recently, we found that muscarinic pretreatment prevents [Ca2+](i) increases from eliciting Cl- secretion in T-84 colonic epithelial cells(4). By studying concomitant inositol phosphate metabolism, ae have now identified D-myo-inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P-4), as the inositol phosphate most likely to mediate this uncoupling. A novel, membrane-permeant ester prepared by total synthesis delivers Ins(3,4,5,6)P-4 intracellularly and confirms that this emerging messenger(5) does inhibit Cl- flux resulting from thapsigargin- or histamine-induced [Ca2+](i) elevations.
引用
收藏
页码:711 / 714
页数:4
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