Stimulation of histamine H1 receptors initiates the hydrolysis of phosphatidylinositides and results in the production of inositol (1, 4,5)-triphosphate and intracellular Ca2+ mobilization. Although the mechanism for signal transduction via the H1 recptor has been extensively investigated, little is known about the correlation between the sensitivity of histamine-induced Ca2+ mobilization and the density of H1 receptors in cultured cells. Cytosolic free Ca2+ concentration ([Ca2+]i) after stimulation by histamine was monitored in single CHO and rat C6-glioma cells stably expressed with H1 receptors and astrocytoma 1321N1 cells using the Ca2+-sensitive dye Indo-1 and dynamic single cell imaging techniques (ACAS 570 laser cytometer). Both of the H1 receptor-expressed CHO cells and C6-glioma cells were over 10 times more sensitive to histamine than astrocytoma 1321N1 cells in which H1 receptors were naturally present. The density of H1 receptors in the transfected cells was also more than 10-fold that of 1321N1 cells. In addition, inhibition of intracellular Ca2+-ATPase by thapsigargin elicited an increase in [Ca2+]i in H1 receptor-overexpessed cells and astrocytoma 1321N1 cells with similar sensitivity. These data suggest that the sensitivity of Ca2+ mobilization by histamine in these cells was correlatively augmented with the increase in the density of H1 receptors.

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