Morita K, Teraoka K, Azuma M, Oka M, Hamano S
Department of Pharmacology, Tokushima University School of Medicine, Japan.
Mol Pharmacol. 1991 Jul;40(1):112-7.
The effects of the tetrodotoxin-insensitive Na+ channel activator palytoxin on both the secretion of endogenous catecholamines and the formation of 14C-catecholamines from [14C]tyrosine were examined using cultured bovine adrenal chromaffin cells. Palytoxin was shown to cause the stimulation of catecholamine secretion in a concentration-dependent manner. However, this toxin caused the reduction rather than the stimulation of 14C-catecholamine formation at the same concentrations. Palytoxin failed to cause any alteration in the activity of tyrosine hydroxylase prepared from bovine adrenal medulla. Furthermore, the uptake of [14C]tyrosine into the cells was shown to be inhibited by this toxin under the conditions in which the suppression of 14C-catecholamine formation was observed, and this inhibitory action on tyrosine uptake was closely correlated with that on catecholamine formation. The inhibitory action of palytoxin on tyrosine uptake into the cells was observed to be noncompetitive, and this effect was not altered by the removal of Na+ from the incubation mixture. These results suggest that palytoxin may be able to inhibit the uptake of [14C]tyrosine into the cells, resulting in the suppression of 14C-catecholamine formation, probably through its direct action on the plasma membranes of bovine adrenal chromaffin cells.
使用培养的牛肾上腺嗜铬细胞，研究了对河豚毒素不敏感的钠离子通道激活剂岩沙海葵毒素对内源性儿茶酚胺分泌以及由[14C]酪氨酸形成14C - 儿茶酚胺的影响。结果表明，岩沙海葵毒素以浓度依赖的方式刺激儿茶酚胺分泌。然而，在相同浓度下，该毒素导致14C - 儿茶酚胺形成减少而非增加。岩沙海葵毒素对从牛肾上腺髓质制备的酪氨酸羟化酶的活性没有引起任何改变。此外，在观察到14C - 儿茶酚胺形成受到抑制的条件下，该毒素被证明会抑制[14C]酪氨酸进入细胞，并且这种对酪氨酸摄取的抑制作用与对儿茶酚胺形成的抑制作用密切相关。观察到岩沙海葵毒素对细胞摄取酪氨酸的抑制作用是非竞争性的，并且通过从孵育混合物中去除钠离子，这种作用并未改变。这些结果表明，岩沙海葵毒素可能能够抑制[14C]酪氨酸进入细胞，从而可能通过其对牛肾上腺嗜铬细胞质膜的直接作用导致14C - 儿茶酚胺形成受到抑制。
