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

Abstract

ABSTRACT

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 μM), serotonin (100 μM) and histamine (200 μM) markedly increased the [Ca²⁺]_i of retina cells by 165%, 126% and 58%, respectively. Tet 30 μM significantly inhibited the increase of [Ca²⁺]_i induced by glutamate (100 μM), serotonin (100 μM) and histamine (200 μM) by 28.0%, 46.8% and 29.0%, respectively. A lower concentration (10 μM) of Tet also produced an inhibitory effect on the increase of [Ca²⁺]_i but was less effective than the Tet 30 μM. In Ca²⁺-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.