Tamburini R, Albuquerque E X, Daly J W, Kauffman F C
J Neurochem. 1981 Sep;37(3):775-80. doi: 10.1111/j.1471-4159.1982.tb12554.x.
Pumiliotoxins (PTX) A, B, and 251D, members of a new class of indolizidine alkaloids isolated from the skin of poison frogs of the family Dendrobatidae, inhibit Ca2+-ATPase activity in sarcoplasmic reticulum vesicles from frog and rat hind-limb muscles. PTX-B and PTX-A appear to be relatively specific inhibitors of Ca2+-ATPase; PTX-A is much less potent than PTX-B. PTX-251D is a potent inhibitor of Ca2+-ATPase, and was also found to inhibit Na+, K+, and Mg2+-ATPases in rat brain synaptosomes. Caffeine and verapamil, two drugs known to affect calcium translocation, are very weak inhibitors of the Ca2+-ATPase. The Ki values for inhibition of the Ca2+-ATPase of rat and frog sarcoplasmic reticulum by PTX-B were comparable and ranged between 22 and 36 microM. Inhibition of calcium-dependent ATPase in sarcoplasmic reticulum by pumiliotoxin-B is noncompetitive with calcium and is not readily reversible. Based on structure-activity profiles, it is concluded that inhibition of Ca2+-ATPase by the indolizidine alkaloids is responsible for the alkaloid-elicited prolongation of twitch in intact muscle.
从箭毒蛙科毒蛙皮肤中分离出的一类新型吲哚里西啶生物碱成员——箭毒蛙毒素（PTX）A、B和251D，可抑制青蛙和大鼠后肢肌肉肌浆网囊泡中的Ca2 + -ATP酶活性。PTX - B和PTX - A似乎是Ca2 + -ATP酶的相对特异性抑制剂；PTX - A的效力远低于PTX - B。PTX - 251D是Ca2 + -ATP酶的强效抑制剂，还被发现可抑制大鼠脑突触体中的Na +、K +和Mg2 + -ATP酶。咖啡因和维拉帕米这两种已知会影响钙转运的药物，是Ca2 + -ATP酶的非常弱的抑制剂。PTX - B对大鼠和青蛙肌浆网Ca2 + -ATP酶抑制作用的Ki值相当，范围在22至36微摩尔之间。箭毒蛙毒素 - B对肌浆网中钙依赖性ATP酶的抑制作用与钙无竞争性，且不易逆转。根据构效关系图谱，得出结论：吲哚里西啶生物碱对Ca2 + -ATP酶的抑制作用是生物碱引起完整肌肉抽搐延长的原因。
