抄録
In cardiovascular system, serotonin (5-hydroxytryptanune; 5-HT) induces very strong vasoconstriction, which is considered to be associated with hypertension or vasospasm. Intracellular calcium ions play a key role as second messenger in the regulation of vasoconstriction. In the present study, we investigated the effect of Ni2+, a cation chenel inhibitor, on 5-HT-induced increase in intracellular calcium concentration ([Ca2+]i) using cultured rat aortic smooth muscle cells (VSMCs). VSMCs were obtained by collagenase digestion and seeded on coverglass. Cells were cultured in 95% air and 5% C02 for 8-10 days in Dulbecco's MEM containing 10% fetal calf serum. [Ca2+]i was measured by a fluorescence spectrophotometer using fura-2. 5-HT (10 μM) caused a biphasic increase in [Ca2+]i of VSMCs, i.e., transient and tonic increase. Ni2+ (1 mM) significantly inhibited the tonic increase, but had no effect on the transient increase. Ni2+ also suppressed 5-HT-induced increase in IP3 content, suggesting that extracellular calcium influx is involved in the transient increase, in addition to the release from intracellular stores. However, Ni2+ completely inhibited calcium influx through voltagedependent calcium channel induced by high KCl (80 mM). Also, Ni2+ significantly inhibited calcium influx induced by thapsigargin (1 μM). These results suggest that 5-HT induces transient calcium influx through Ni2+ -sensitive calcium channel, which is distinct from voltage-dependent, capacitative or second messengeroperated calcium channels.
