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Histamine H 3 receptor‐mediated inhibition of depolarization‐induced, dopamine D 1 receptor‐dependent release of [ 3 H]‐γ‐aminobutyric acid from rat striatal slices
A study was made of the regulation of [ 3 H]‐γ‐aminobutyric acid ([ 3 H]‐GABA) release from slices of rat striatum by endogenous dopamine and exogenous histamine and a histamine H 3 ‐agonist. Depolarization‐induced release of [ 3 H]‐GABA was Ca 2+ ‐dependent and was increased in the presence of the...
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Published in: | British journal of pharmacology 2009-01, Vol.133 (1), p.165-171 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | A study was made of the regulation of [
3
H]‐γ‐aminobutyric acid ([
3
H]‐GABA) release from slices of rat striatum by endogenous dopamine and exogenous histamine and a histamine H
3
‐agonist. Depolarization‐induced release of [
3
H]‐GABA was Ca
2+
‐dependent and was increased in the presence of the dopamine D
2
receptor family antagonist, sulpiride (10 μ
M
). The sulpiride‐potentiated release of [
3
H]‐GABA was strongly inhibited by the dopamine D
1
receptor family antagonist, SCH 23390 (1 μ
M
). Neither antagonist altered basal release.
The 15 m
M
K
+
‐induced release of [
3
H]‐GABA in the presence of sulpiride was inhibited by 100 μ
M
histamine (mean inhibition 78±3%) and by the histamine H
3
receptor‐selective agonist, immepip, 1 μ
M
(mean inhibition 81±5%). The IC
50
values for histamine and immepip were 1.3±0.2 μ
M
and 16±2 n
M
, respectively. The inhibitory effects of histamine and immepip were reversed by the H
3
receptor antagonist, thioperamide, 1 μ
M
.
The inhibition of 15 m
M
K
+
‐induced [
3
H]‐GABA release by immepip was reversed by the H
3
receptor antagonist, clobenpropit, K
d
0.11±0.04 n
M
. Clobenpropit alone had no effect on basal or stimulated release of [
3
H]‐GABA.
Elevated K
+
caused little release of [
3
H]‐GABA from striatal slices from reserpinized rats, unless the D
1
partial agonist, R(+)‐SKF 38393, 1 μ
M
, was also present. The stimulated release in the presence of SKF 38393 was reduced by 1 μ
M
immepip to the level obtained in the absence of SKF 38393.
These observations demonstrate that histamine H
3
receptor activation strongly inhibits the dopamine D
1
receptor‐dependent release of [
3
H]‐GABA from rat striatum; primarily through an interaction at the terminals of GABA neurones.
British Journal of Pharmacology
(2001)
133
, 165–171; doi:
10.1038/sj.bjp.0704053 |
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ISSN: | 0007-1188 1476-5381 |
DOI: | 10.1038/sj.bjp.0704053 |