PHARMACOLOGICAL EVIDENCE FOR AN OMEGA-CONOTOXIN, DIHYDROPYRIDINE-INSENSITIVE NEURONAL CA2+ CHANNEL

被引:58
作者
LUNDY, PM
FREW, R
FULLER, TW
HAMILTON, MG
机构
[1] Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Alta.
来源
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION | 1991年 / 206卷 / 01期
关键词
OMEGA-CONOTOXIN GVIA; ACETYLCHOLINE RELEASE; CA2+ INFLUX; CA2+ (INTRACELLULAR FREE); VOLTAGE-SENSITIVE CA2+ CHANNELS;
D O I
10.1016/0922-4106(91)90147-A
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Inactivation of N-type voltage-sensitive Ca2+ channels (VSCC) with omega-conotoxin (omega-CgTx) in tissue obtained from chicken brain produces a concentration dependent (0.01-0.1-mu-M) inhibition of K+-stimulated Ca2+ influx (DELTA-K+), the rise in [Ca2+]i and acetylcholine (ACh) release. In identical preparations from rat brain, Ca2+ influx and the rise in [Ca2+]i were only marginally affected by much higher (1-10-mu-M) concentrations of omega-CgTx. The release of ACh, however, was inhibited to the same degree with similar amounts of omega-CgTx as those used in chicken brain. An L-type VSCC inhibitor failed to affect any of these parameters alone, or to augment the effect of omega-CgTx. The results suggest that almost all the VSCC in chicken brain are of the N type and that these channels regulate neurotransmitter release. In rat brain, on the other hand, Ca2+ channels resistant to N- or L-type blockers account for almost 75% of the measurable Ca2+ influx and rise in [Ca2+]i. The conspicuous dissociation between the regulation of Ca2+ influx and ACh release demonstrated in rat brain by using omega-CgTx, suggest that neurotransmitter release is governed by only a small proportion of strategically located N-type, omega-CgTx sensitive, VSCC in the presynaptic terminal.
引用
收藏
页码:61 / 68
页数:8
相关论文
共 29 条
[1]  
AHMAD SN, 1988, BRAIN RES, V453, P247
[2]   OMEGA-AGA-I - A PRESYNAPTIC CALCIUM-CHANNEL ANTAGONIST FROM VENOM OF THE FUNNEL WEB SPIDER, AGELENOPSIS-APERTA [J].
BINDOKAS, VP ;
ADAMS, ME .
JOURNAL OF NEUROBIOLOGY, 1989, 20 (04) :171-188
[3]   EFFECTS OF POTASSIUM, VERATRIDINE AND SCORPION-VENOM ON CALCIUM ACCUMULATION AND TRANSMITTER RELEASE BY NERVE-TERMINALS INVITRO [J].
BLAUSTEIN, MP .
JOURNAL OF PHYSIOLOGY-LONDON, 1975, 247 (03) :617-655
[4]  
Bradford M.M., 1968, ANAL BIOCHEM, V72, P48
[5]   EFFECTS OF CA-2+ CHANNEL BLOCKERS ON CA-2+ TRANSLOCATION ACROSS SYNAPTOSOMAL MEMBRANES [J].
CARVALHO, CAM ;
COUTINHO, OP ;
CARVALHO, AP .
JOURNAL OF NEUROCHEMISTRY, 1986, 47 (06) :1774-1784
[6]   INHIBITION OF CENTRAL NEUROTRANSMITTER RELEASE BY OMEGA-CONOTOXIN GVIA, A PEPTIDE MODULATOR OF THE N-TYPE VOLTAGE-SENSITIVE CALCIUM-CHANNEL [J].
DOOLEY, DJ ;
LUPP, A ;
HERTTING, G .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1987, 336 (04) :467-470
[7]   OMEGA-CONOTOXIN GVIA AND PHARMACOLOGICAL MODULATION OF HIPPOCAMPAL NORADRENALINE RELEASE [J].
DOOLEY, DJ ;
LUPP, A ;
HERTTING, G ;
OSSWALD, H .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1988, 148 (02) :261-267
[8]   OMEGA-CONOTOXIN GVIA BLOCKS SYNAPTIC TRANSMISSION IN THE CA1 FIELD OF THE HIPPOCAMPUS [J].
DUTAR, P ;
RASCOL, O ;
LAMOUR, Y .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1989, 174 (2-3) :261-266
[9]  
GRAY WR, 1988, ANNU REV BIOCHEM, V57, P665, DOI 10.1146/annurev.bi.57.070188.003313
[10]  
GRYNKIEWICZ G, 1985, J BIOL CHEM, V260, P3440