Article date: May 2001
By: J‐A Arias‐Montaño, B Floran, M Garcia, J Aceves, J M Young in Volume 133, Issue 1, pages 165-171
A study was made of the regulation of [3H]‐γ‐aminobutyric acid ([3H]‐GABA) release from slices of rat striatum by endogenous dopamine and exogenous histamine and a histamine H3‐agonist. Depolarization‐induced release of [3H]‐GABA was Ca2+‐dependent and was increased in the presence of the dopamine D2 receptor family antagonist, sulpiride (10 μM). The sulpiride‐potentiated release of [3H]‐GABA was strongly inhibited by the dopamine D1 receptor family antagonist, SCH 23390 (1 μM). Neither antagonist altered basal release.
The 15 mM K+‐induced release of [3H]‐GABA in the presence of sulpiride was inhibited by 100 μM histamine (mean inhibition 78±3%) and by the histamine H3 receptor‐selective agonist, immepip, 1 μM (mean inhibition 81±5%). The IC50 values for histamine and immepip were 1.3±0.2 μM and 16±2 nM, respectively. The inhibitory effects of histamine and immepip were reversed by the H3 receptor antagonist, thioperamide, 1 μM.
The inhibition of 15 mM K+‐induced [3H]‐GABA release by immepip was reversed by the H3 receptor antagonist, clobenpropit, Kd 0.11±0.04 nM. Clobenpropit alone had no effect on basal or stimulated release of [3H]‐GABA.
Elevated K+ caused little release of [3H]‐GABA from striatal slices from reserpinized rats, unless the D1 partial agonist, R(+)‐SKF 38393, 1 μM, was also present. The stimulated release in the presence of SKF 38393 was reduced by 1 μM immepip to the level obtained in the absence of SKF 38393.
These observations demonstrate that histamine H3 receptor activation strongly inhibits the dopamine D1 receptor‐dependent release of [3H]‐GABA from rat striatum; primarily through an interaction at the terminals of GABA neurones.
A study was made of the regulation of [3H]‐γ‐aminobutyric acid ([3H]‐GABA) release from slices of rat striatum by endogenous dopamine and exogenous histamine and a histamine H3‐agonist. Depolarization‐induced release of [3H]‐GABA was Ca2+‐dependent and was increased in the presence of the dopamine D2 receptor family antagonist, sulpiride (10 μM). The sulpiride‐potentiated release of [3H]‐GABA was strongly inhibited by the dopamine D1 receptor family antagonist, SCH 23390 (1 μM). Neither antagonist altered basal release.
The 15 mM K+‐induced release of [3H]‐GABA in the presence of sulpiride was inhibited by 100 μM histamine (mean inhibition 78±3%) and by the histamine H3 receptor‐selective agonist, immepip, 1 μM (mean inhibition 81±5%). The IC50 values for histamine and immepip were 1.3±0.2 μM and 16±2 nM, respectively. The inhibitory effects of histamine and immepip were reversed by the H3 receptor antagonist, thioperamide, 1 μM.
The inhibition of 15 mM K+‐induced [3H]‐GABA release by immepip was reversed by the H3 receptor antagonist, clobenpropit, Kd 0.11±0.04 nM. Clobenpropit alone had no effect on basal or stimulated release of [3H]‐GABA.
Elevated K+ caused little release of [3H]‐GABA from striatal slices from reserpinized rats, unless the D1 partial agonist, R(+)‐SKF 38393, 1 μM, was also present. The stimulated release in the presence of SKF 38393 was reduced by 1 μM immepip to the level obtained in the absence of SKF 38393.
These observations demonstrate that histamine H3 receptor activation strongly inhibits the dopamine D1 receptor‐dependent release of [3H]‐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
DOI: 10.1038/sj.bjp.0704053
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