EFFECT OF AN INTRACELLULAR CALCIUM CHELATOR ON THE REGULATION OF ELECTRICALLY EVOKED [H-3] NORADRENALINE RELEASE FROM RAT HIPPOCAMPAL SLICES

被引:18
作者
FREDHOLM, BB
HU, PS
机构
[1] Department of Pharmacology, Karolinska Institutet, Stockholm, S-104 01
关键词
CALCIUM CHELATOR; PRESYNAPTIC RECEPTORS; CALCIUM CHANNELS; CONOTOXIN; ADENOSINE RECEPTORS; ALPHA(2)-ADRENOCEPTORS;
D O I
10.1111/j.1476-5381.1993.tb13451.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The electrically (3 Hz, 5 min) evoked [H-3]-noradrenaline ([H-3]-NA) release from rat hippocampal slices was reduced by prior treatment of the slices with 1,2-bis(2-aminophenoxy)ethane-N,N,N'N'-tetraacetomethylester (BAPTA/AM) in a concentration-(10 to 500 muM) dependent manner (40% at 30 muM). Reduction of medium calcium from 1.3 to 0.5 mM caused a larger (70%) decrease. BAPTA free acid (100 mM), a non-permeable Ca2+-chelator had no significant effect. 2 Basal [H-3]-noradrenaline release was reduced by BAPTA/AM in a concentration-dependent manner (50% at 30 muM), but reduction of external Ca2+ from 1.3 to 0.5 mM did not alter basal release. 3 About 10% of total [H-3]-NA in the slices was released at 3 Hz stimulation in 1.3 mM Ca2+ buffer. Addition of the alpha2-adrenoceptor antagonist, idazoxan (1 muM), increased electrically evoked [H-3]-NA release to 26% but stimulated release was not altered by the adenosine A1-receptor antagonist, 8-cyclopentyl theophylline (8-CPT) (1 muM). 4 Evoked release was reduced by the alpha2-receptor agonist, UK 14,304, in a concentration-dependent manner in the presence of 8-CPT (1 muM). The magnitude of this effect was not altered by the treatment of slices with 30 muM BAPTA/AM. 5 The adenosine A, receptor agonist, N6-cyclohexyl adenosine (CHA) (1 muM) inhibited electrically evoked [H-3]-NA release by about 40% in the presence of idazoxan (1 muM). The effect of CHA was not significantly altered by treatment of slices with BAPTA/AM. 6 The N-type Ca2+-channel antagonist, omega-conotoxin (30 nM), inhibited electrically evoked [H-3]-NA release by 30-50% and this was not altered by treatment of the slices with BAPTA/AM. 7 The present results show that spontaneous [H-3]-NA release is affected by reduction of intracellular Ca2+, but not by reduction of extracellular Ca2+ or by the presynaptic agonists or omega-conotoxin. By contrast, electrically evoked release was affected more strongly by alterations of extracellular Ca2+ than by buffering intracellular Ca2+. The reduction of electrically evoked [H-3]-NA release by agonists at the adenosine A1-receptor and alpha2-adrenoceptor is probably mediated through the control of Ca2+ entry via membrane ion channels or at a low affinity Ca2+-site governing evoked release.
引用
收藏
页码:126 / 131
页数:6
相关论文
共 37 条
[1]   INHIBITORS OF CALCIUM BUFFERING DEPRESS EVOKED TRANSMITTER RELEASE AT THE SQUID GIANT SYNAPSE [J].
ADAMS, DJ ;
TAKEDA, K ;
UMBACH, JA .
JOURNAL OF PHYSIOLOGY-LONDON, 1985, 369 (DEC) :145-159
[2]  
ADLER EM, 1991, J NEUROSCI, V11, P1496
[3]   THE CALCIUM SIGNAL FOR TRANSMITTER SECRETION FROM PRESYNAPTIC NERVE-TERMINALS [J].
AUGUSTINE, GJ ;
ADLER, EM ;
CHARLTON, MP .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES-SERIES, 1991, 635 :365-381
[4]   CALCIUM ACTION IN SYNAPTIC TRANSMITTER RELEASE [J].
AUGUSTINE, GJ ;
CHARLTON, MP ;
SMITH, SJ .
ANNUAL REVIEW OF NEUROSCIENCE, 1987, 10 :633-693
[6]  
CHARLTON M P, 1986, Society for Neuroscience Abstracts, V12, P817
[7]  
DELANEY K, 1991, J NEUROSCI, V11, P2631
[8]   HOW DOES ADENOSINE INHIBIT TRANSMITTER RELEASE [J].
FREDHOLM, BB ;
DUNWIDDIE, TV .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1988, 9 (04) :130-134
[9]   ROLE OF G-PROTEINS, CYCLIC-AMP, AND ION CHANNELS IN THE INHIBITION OF TRANSMITTER RELEASE BY ADENOSINE [J].
FREDHOLM, BB ;
DUNERENGSTROM, M ;
FASTBOM, J ;
HU, PS ;
VANDERPLOEG, I .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1990, 604 :276-288
[10]   2-CHLOROADENOSINE REDUCES THE N-CALCIUM CURRENT OF CULTURED MOUSE SENSORY NEURONS IN A PERTUSSIS TOXIN-SENSITIVE MANNER [J].
GROSS, RA ;
MACDONALD, RL ;
RYANJASTROW, T .
JOURNAL OF PHYSIOLOGY-LONDON, 1989, 411 :585-595