INHIBITION BY ZN2+ OF URIDINE 5'-TRIPHOSPHATE-INDUCED CA2+-INFLUX BUT NOT CA2+-MOBILIZATION IN RAT PHEOCHROMOCYTOMA CELLS

被引:33
作者
KOIZUMI, S [1 ]
NAKAZAWA, K [1 ]
INOUE, K [1 ]
机构
[1] NATL INST HLTH SCI, DIV PHARMACOL, TOKYO 158, JAPAN
关键词
URIDINE 5'-TRIPHOSPHATE (UTP); INTRACELLULAR CA2+ CONCENTRATION; DOPAMINE RELEASE; ZN2+; PC12; CELLS; CA2+-INFLUX;
D O I
10.1111/j.1476-5381.1995.tb16643.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 Uridine 5'-triphosphate (UTP)-evoked increase in intracellular Ca2+ concentration ([Ca](i)) and release of dopamine were investigated in rat phaeochromocytoma PC12 cells. UTP (1-100 mu M) evoked an increase in [Ca](i) in a concentration-dependent manner. This response was decreased to about 30% by extracellular Ca2+-depletion, but not abolished. This [Ca](i) rise was mimicked by 100 mu M ATP but not by 100 mu M 2-methyl-thio-ATP or alpha,beta-methylene-ATP in the absence of external Ca2+, suggesting that the response was mediated by P-2u purinoceptors, a subclass of P-2-purinoceptors. 2 The UTP-evoked [Ca](i) rise consisted of two components; a transient and a sustained one. When external Ca2+ was removed, the sustained component was abolished while the transient component was decreased by about 70% but did not disappear. These results suggest that UTP induces Ca2+-mobilization and, subsequently, Ca2+-influx. 3 The UTP-evoked increase in [Ca](i) was not affected by Cd2+ (100 and 300 mu M) or nicardipine (30 mu M), inhibitors of voltage-gated calcium channels, but was significantly inhibited by Zn2+ (10-300 mu M) in the presence of external Ca2+, Zn2+, however, did not affect the Ca2+ response to UTP in the absence of external Ca2+. 4 UTP (30 mu M-1 mM) evoked the release of dopamine from the cells in a concentration-dependent manner. This dopamine release was abolished by Ca2+-depletion or Zn2+ but not by Cd2+ or nicardipine. 5 Taken together, the data demonstrate that UTP stimulates P-2U-purinoceptors and induces a rise in [Ca](i) both by Ca2+-mobilization and Ca2+-influx in PC12 cells. The dopamine release evoked by UTP requires external Ca2+ which may enter the cells through pathways sensitive to Zn2+ but insensitive to Cd2+ or nicardipine.
引用
收藏
页码:1502 / 1508
页数:7
相关论文
共 39 条
[1]   PURINOCEPTORS - ARE THERE FAMILIES OF P2X AND P2Y PURINOCEPTORS [J].
ABBRACCHIO, MP ;
BURNSTOCK, G .
PHARMACOLOGY & THERAPEUTICS, 1994, 64 (03) :445-475
[2]  
BARRY VA, 1994, J CELL SCI, V107, P451
[3]   PHARMACOLOGY AND ELECTROPHYSIOLOGY OF ATP-ACTIVATED ION CHANNELS [J].
BEAN, BP .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1992, 13 (03) :87-90
[4]   NEW STRUCTURAL MOTIF FOR LIGAND-GATED ION CHANNELS DEFINED BY AN IONOTROPIC ATP RECEPTOR [J].
BRAKE, AJ ;
WAGENBACH, MJ ;
JULIUS, D .
NATURE, 1994, 371 (6497) :519-523
[5]   IS THERE A BASIS FOR DISTINGUISHING 2 TYPES OF P2-PURINOCEPTOR [J].
BURNSTOCK, G ;
KENNEDY, C .
GENERAL PHARMACOLOGY, 1985, 16 (05) :433-440
[6]  
CLEMENTI E, 1992, J BIOL CHEM, V267, P2164
[7]   ZN2+ POTENTIATES ATP-ACTIVATED CURRENTS IN RAT SYMPATHETIC NEURONS [J].
CLOUES, R ;
JONES, S ;
BROWN, DA .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1993, 424 (02) :152-158
[8]  
DESOUZA LR, 1995, IN PRESS J NEUROSCI
[9]   ATP RECEPTOR-MEDIATED SYNAPTIC CURRENTS IN THE CENTRAL-NERVOUS-SYSTEM [J].
EDWARDS, FA ;
GIBB, AJ ;
COLQUHOUN, D .
NATURE, 1992, 359 (6391) :144-147
[10]   ATP MEDIATES FAST SYNAPTIC TRANSMISSION IN MAMMALIAN NEURONS [J].
EVANS, RJ ;
DERKACH, V ;
SURPRENANT, A .
NATURE, 1992, 357 (6378) :503-505