副腎クロマフィン細胞からのカテコールアミン分泌と薬物作用 : シグナル伝達と細胞機能調節

概要

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The effect of palytoxin (PTX) on catecholamine (CA) secretion from cultured bovine adrenal chromaffin cells was examined. PTX (> 10-10 M) induced CA secretion concentration-dependently. About 40 ?? 50% of the total cellular CA was secreted during a 20 min incubation with 3 × 10-8 M PTX. PTX caused increases in [22Na]+ and [95Ca]2+-influxes into the cells, which were not affected by TTX. PTX-induced CA secretion and [22Na]+ and [45Ca]2+-influxes were significantly inhibited by quinidine and aprindine, antiarrythmic drugs. Ca2+-channel blockers such as nifedipine, verapamil, Co2+, and Cd2+ inhibited both CA secretion and [45Ca]2+-influx induced by PTX. These results indicated that PTXinduced CA secretion was mediated by activation of Na+-dependent, TTX-insensitive voltage-dependent Ca2+-channels. PTX-induced [22Na]+-influx was inhibited by amiloride, an inhibitor of the Na+-H+ exchange system, suggesting that the Na+-H+ exchange mechanism might be involved in PTX-induced [22Na]+-influx into the cells. The effects of flavonoids on CA secretion from permeabilized adrenal chromaffin cells were examined. CA secretion from the cells in response to a direct Ca2+ challenge was inhibited by quercetin (> 10-5 M) and apigenin (> 10-5 M). These flavonoids also inhibited phorbol ester TPA-induced CA secretion. Therefore, the inhibitory effects of flavonoids on CA secretion were thought to be attributed to their inhibitory effects on PKC.