Leite R S, Franco W, Ownby C L, Selistre-de-Araujo H S
Departamento de Ciências Fisiológicas, Universidade Federal de São Carlos, Rodovia Washington Luis km 235, São Carlos, SP 13565-905, Brazil.
Toxicon. 2004 Jan;43(1):77-83. doi: 10.1016/j.toxicon.2003.10.024.
ACL myotoxin (ACLMT) is a Lys49 phospholipase A(2)-like protein isolated from the venom of the snake Agkistrodon contortrix laticinctus. The aim of this work was to study the effect of ACLMT on water transport in the toad bladder. Water flow through the membrane was measured gravimetrically in bag preparations of the bladder. ACLMT (20 nM) increased the baseline water flow and partially inhibited arginine-vasopressin (AVP), 8-chlorophenylthio-cAMP (8-CPT-cAMP) and forskolin-stimulated water flow. The effect of ACLMT on baseline or AVP-stimulated water flow was prevented by lanthanum (0.1 mM) indicating that the effect of ACLMT on water transport may be mediated through an increase in intracellular calcium. The effect of ACLMT on baseline water flow was also prevented by nifedipine (0.1 mM) indicating the participation of exogenous calcium in this effect. Carbachol (0.1 mM) has been shown to enhance baseline water flow while inhibiting AVP-stimulated water flow. The effects of ACLMT and carbachol on baseline water flow and AVP-stimulated water flow were not additive, suggesting that both agents alter water transport by a similar mechanism. Indomethacin (10 microM) reduced the effect of ACLMT on forskolin-stimulated water flow, suggesting an increase in prostaglandin biosynthesis. These results suggest that the effects of ACLMT on water transport may be mediated by increasing intracellular calcium and stimulation prostaglandin biosynthesis.
蝮蛇肌毒素(ACLMT)是一种从宽带水蛇毒液中分离出的类Lys49磷脂酶A2蛋白。本研究的目的是探讨ACLMT对蟾蜍膀胱水转运的影响。通过膀胱袋制备物重量法测量通过膜的水流量。ACLMT(20 nM)增加基础水流量,并部分抑制精氨酸加压素(AVP)、8-氯苯硫基-cAMP(8-CPT-cAMP)和福斯可林刺激的水流量。镧(0.1 mM)可阻止ACLMT对基础或AVP刺激的水流量的影响,表明ACLMT对水转运的影响可能通过细胞内钙增加来介导。硝苯地平(0.1 mM)也可阻止ACLMT对基础水流量的影响,表明外源性钙参与了这一作用。已证明卡巴胆碱(0.1 mM)可增强基础水流量,同时抑制AVP刺激的水流量。ACLMT和卡巴胆碱对基础水流量和AVP刺激的水流量的影响不是相加的,提示这两种药物通过相似的机制改变水转运。吲哚美辛(10 microM)降低了ACLMT对福斯可林刺激的水流量的影响,提示前列腺素生物合成增加。这些结果表明,ACLMT对水转运的影响可能通过增加细胞内钙和刺激前列腺素生物合成来介导。