LU52396, AN INHIBITOR OF THE STORE-DEPENDENT (CAPACITATIVE) CA2+ INFLUX

被引:17
|
作者
CLEMENTI, E
MARTINI, A
STEFANI, G
MELDOLESI, J
VOLPE, P
机构
[1] UNIV MILAN,SCI INST SAN RAFFAELE,DIBIT,I-20132 MILAN,ITALY
[2] UNIV REGGIO CALABRIA,FAC PHARM,CHAIR PHARMACOL,CATANZARO,ITALY
[3] UNIV MILAN,DEPT PHARMACOL,CNR,CTR MOLEC & CELLULAR PHARMACOL,MILAN,ITALY
[4] UNIV MILAN,DEPT PHARMACOL,CNR,B CECCARELLI CTR,MILAN,ITALY
[5] UNIV PADUA,CNR,CTR MUSCLE BIOL & PHYSIOPATHOL,PADUA,ITALY
[6] UNIV MESSINA,INST GEN PATHOL,MESSINA,ITALY
来源
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION | 1995年 / 289卷 / 01期
关键词
CA2+; INFLUX; STORE-DEPENDENT; 2ND-MESSENGER-OPERATED CHANNEL; CA2+ STORE; CA2+ ATPASE; IP3; RECEPTOR; RYANODINE RECEPTOR;
D O I
10.1016/0922-4106(95)90164-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The effects of 1-[2-(4-fluorophenyl)cyclohexyl]-2-[4-(3-phenylalkyl)-piperazin- 1-yl]-ethanol, LU52396, on a) Ca2+ influx across the plasma membrane and b) Ca2+ mobilization from intracellular rapidly-exchanging Ca2+ stores were investigated in HeLa cells and in isolated microsomal fractions derived from the cerebellum and the skeletal muscle. LU52396 was found to be a potent inhibitor (K-i of about 2 mu M) of the Ca2+ influx activated by depletion of intracellular Ca2+ stores, a phenomenon referred to as store-dependent or capacitative Ca2+ influx. Such an effect, which was reversed by cell washing, was mediated neither by a depolarization of the cell, with decrease in the driving force for cation influx, nor by a change of the intracellular pH, and might therefore be due to a direct action of the drug on either the responsible channel in the plasma membrane or, less likely, on its regulatory mechanisms. Additional effects, i.e. inhibition of receptor-mediated Ca2+ influx, of Ca2+ release from intracellular stores via either inositol 1,4,5-trisphosphate or ryanodine receptors, and of Ca2+ reuptake into the stores via sarcoplasmic-endoplasmic reticulum Ca2+-ATPases, were also induced by the drug, however at concentrations 20-fold or more than those effective on the store-dependent influx. To our knowledge LU52396 is the first pharmacological tool that is found to be addressed with some preference to the store-dependent Ca2+ influx. It promises, threfore, to be useful for the characterization of the process, the identification of the responsible channels and, possibly, also of the molecular mechanisms through which these channels operate.
引用
收藏
页码:23 / 31
页数:9
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