Histamine H1 receptor activation stimulates [3H]GABA release from human astrocytoma U373 MG cells.
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.
Soria-Jasso
L E
LE
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, México, D.F., México.
Arias-Montaño
J A
JA
D001254:Astrocytoma; D002118:Calcium / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D011969:Receptors, Histamine H1 / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D007295:Inositol Phosphates; D011969:Receptors, Histamine H1; D014316:Tritium; D005680:gamma-Aminobutyric Acid; D006632:Histamine; D002118:Calcium