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Effect of an intracellular calcium chelator on the regulation of electrically evoked [ 3 H]‐noradrenaline release from rat hippocampal slices
Author(s) -
Fredholm Bertil B.,
Hu PingSheng
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13451.x
Subject(s) - bapta , idazoxan , chemistry , agonist , adenosine , endocrinology , medicine , stimulation , calcium , egta , adenosine receptor antagonist , antagonist , biophysics , adenosine receptor , receptor , biochemistry , biology , prazosin , organic chemistry
1 The electrically (3 Hz, 5 min) evoked [ 3 H]‐noradrenaline ([ 3 H]‐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 μ m ) dependent manner (40% at 30 μ m ). Reduction of medium calcium from 1.3 to 0.5 m m caused a larger (70%) decrease. BAPTA free acid (100 m m ), a non‐permeable Ca 2+ ‐chelator had no significant effect. 2 Basal [ 3 H]‐noradrenaline release was reduced by BAPTA/AM in a concentration‐dependent manner (50% at 30 μ m ), but reduction of external Ca 2+ from 1.3 to 0.5 m m did not alter basal release. 3 About 10% of total [ 3 H]‐NA in the slices was released at 3 Hz stimulation in 1.3 m m Ca 2+ buffer. Addition of the α 2 ‐adrenoceptor antagonist, idazoxan (1 μ m ), increased electrically evoked [ 3 H]‐NA release to 26% but stimulated release was not altered by the adenosine A 1 ‐receptor antagonist, 8‐cyclopentyl theophylline (8‐CPT) (1 μ m ). 4 Evoked release was reduced by the α 2 ‐receptor agonist, UK 14,304, in a concentration‐dependent manner in the presence of 8‐CPT (1 μ m ). The magnitude of this effect was not altered by the treatment of slices with 30 μ m BAPTA/AM. 5 The adenosine A 1 receptor agonist, N 6 ‐cyclohexyl adenosine (CHA) (1 μ m ) inhibited electrically evoked [ 3 H]‐NA release by about 40% in the presence of idazoxan (1 μ m ). The effect of CHA was not significantly altered by treatment of slices with BAPTA/AM. 6 The N‐type Ca 2+ ‐channel antagonist, ω‐conotoxin (30 n m ), inhibited electrically evoked [ 3 H]‐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 [ 3 H]‐NA release is affected by reduction of intracellular Ca 2+ , but not by reduction of extracellular Ca 2+ or by the presynaptic agonists or ω‐conotoxin. By contrast, electrically evoked release was affected more strongly by alterations of extracellular Ca 2+ than by buffering intracellular Ca 2+ . The reduction of electrically evoked [ 3 H]‐NA release by agonists at the adenosine A 1 ‐receptor and α 2 ‐adrenoceptor is probably mediated through the control of Ca 2+ entry via membrane ion channels or at a low affinity Ca 2+ ‐site governing evoked release.