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  • Title: Histamine H1 receptor activation stimulates [3H]GABA release from human astrocytoma U373 MG cells.
    Author: Soria-Jasso LE, Arias-Montaño JA.
    Journal: Eur J Pharmacol; 1996 Dec 27; 318(1):185-92. PubMed ID: 9007531.
    Abstract:
    In U373 MG cells, a line derived from a human astrocytoma, histamine stimulated the release of [3H]gamma-aminobutyric acid ([3H]GABA) in a concentration-dependent manner (286 +/- 23% of basal release at 1 mM histamine). Neither Ca2+ removal nor Cd2+ (100 microM) affected [3H]GABA release evoked by 100 microM histamine but the response was significantly reduced by 10 microM U-73122 ({1-[6-((17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl)-amino)-hexyl]-1 H-pyrrole-2,5-dione}), an inhibitor of phospholipase C activation (79 +/- 8% inhibition) and by 10 microM dimethylbenzamil, a selective blocker of plasma membrane Na+/Ca2+ exchange (58 +/- 6% inhibition). In [3H]inositol-labelled cells histamine stimulated [3H]inositol phosphate accumulation (EC50, 17 +/- 2 microM; maximum effect, 203 +/- 4% of basal). Histamine-evoked Ca2+ mobilisation yielded an EC50 of 12 +/- 2 microM and maximum delta[Ca2+]i of 337 +/- 23 nM. Thapsigargin (1 nM) increased [Ca2+]i (delta[Ca2+]i 164 +/- 12 nM) and prevented any further increase by histamine (100 microM). The effects of histamine on [3H]GABA release, [3H]inositol phosphate accumulation and Ca2+ mobilisation were blocked by the selective histamine H1 receptor antagonist mepyramine. Taken together, these results indicate that histamine stimulates [3H]GABA release by increasing [Ca2+]i. The mechanism of release may be related to changes in transmembranal Na+ gradients and reversal of GABA carrier transport due to stimulation of plasma membrane Na+/Ca2+ exchange.
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