Inhibitory Effects of Tetrandrine on Intracellular Free Ca 2+ Increase Induced by Glutamate, Serotonin and Histamine in Dissociated Retina Cells

The effects of tetrandrine (Tet) on the elevation of intracellular free Ca2+ concentration ([Ca2+]i) induced by glutamate, serotonin and histamine in dissociated rabbit retina cells were studied. The changes of [Ca2+]i were reflected by the fluorescent indicator, Fura-2/AM, employed. In the presence of extracellular Ca2+ (1.3 mM), glutamate, serotonin and histamine significantly increased the [Ca2+]i in a dose-dependent manner. Glutamate (100 microM), serotonin (100 microM) and histamine (200 microM) markedly increased the [Ca2+]i of retina cells by 165%, 126% and 58%, respectively. Tet 30 microM significantly inhibited the increase of [Ca2+]i induced by glutamate (100 microM), serotonin (100 microM) and histamine (200 microM) by 28.0%, 46.8% and 29.0%, respectively. A lower concentration (10 microM) of Tet also produced an inhibitory effect on the increase of [Ca2+]i but was less effective than the Tet 30 microM. In Ca(2+)-free Hank's solution, Tet did not produce a significant inhibitory effect on the increase of [Ca2+]i caused by serotonin and histamine. These results indicate that Tet exercises blocking Ca2+ influx from the extracellular site via NMDA, 5-HT2 and H1-receptor operated Ca2+ channels and has no obvious effect on the Ca2+ release from intracellular Ca2+ stores.