α1-adrenoceptors trigger the snake venom production cycle in secretory cells by activating phosphatidylinositol 4,5-bisphosphate hydrolysis and ERK signaling pathway
α1-adrenoceptors trigger the snake venom production cycle in secretory cells by activating phosphatidylinositol 4,5-bisphosphate hydrolysis and ERK signaling pathway
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DOI：
10.1016/j.cbpa.2008.04.607
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发表时间：
2008-08-01
影响因子：
2.3
通讯作者：
Yamanouye, Norma
中科院分区：
文献类型：
--
作者：
Kerchove, Celine M.;Luna, Milene S. A.;Yamanouye, Norma
在咬伤或人工提取后，毒液腺中的毒液损失导致毒液分泌细胞的形态变化和新毒液产生周期的开始。我们以前已经表明，刺激α-和β-肾上腺素能受体的分泌细胞的毒液腺是必不可少的开始的毒液生产周期Bothrops jararaca。我们研究了α（1）-肾上腺素受体启动毒液产生周期的信号通路。结果表明，α（1）肾上腺素能受体亚型存在于蛇的毒腺。在静止期细胞中，用苯肾上腺素刺激α（1）-肾上腺素受体可增加总磷酸肌醇浓度，这种作用可被磷脂酶C抑制剂U 73122阻断。苯乙醯胺从毒胡萝卜素敏感的贮藏物中调动Ca 2+，并增加蛋白激酶C活性。此外，α 1肾上腺素受体刺激增加ERK 1/2的活性，部分通过蛋白激酶C。用RTPCR方法获得了一条蛇α（1）-肾上腺素能受体的部分序列（260 bp），该序列与不同物种的α（1）-和α（1B）-肾上腺素能受体具有较高的同源性。这些结果表明，α（1）-肾上腺素受体在毒液分泌细胞可能耦合到G（q）蛋白，并触发毒液生产周期通过激活磷脂酰肌醇4，5-二磷酸和ERK信号通路。(c)2008年爱思唯尔公司All rights reserved.
Loss of venom from the venom gland after biting or manual extraction leads to morphological changes in venom secreting cells and the start of a cycle of production of new venom. We have previously shown that stimulation of both (alpha- and beta-adrenoceptors in the secretory cells of the venom gland is essential for the onset of the venom production cycle in Bothrops jararaca. We investigated the signaling pathway by which the alpha(1)-adrenoceptor initiates the venom production cycle. Our results show that the alpha(1)-adrenoceptor subtype is present in venom gland of the snake. In quiescent cells, stimulation of alpha(1)-adrenoceptor with phenylephrine increased the total inositol phosphate concentration, and this effect was blocked by the phospholipase C inhibitor U73122. Phenylephrine mobilized Ca2+ from thapsigargin-sensitive stores and increased protein kinase C activity. In addition, alpha(1)-adrenoceptor stimulation increased the activity of ERK 1/2, partially via protein kinase C. Using RTPCR approach we obtained a partial sequence of a snake alpha(1)-adrenoceptor (260 bp) with higher identity with alpha(1)- and alpha(1B)-adrenoceptor from different species. These results suggest that alpha(1)-adrenoceptor in the venom secreting cells are probably coupled to a G(q) protein and trigger the venom production cycle by activating the phosphatidylinositol 4,5-bisphosphate and ERK signaling pathway. (c) 2008 Elsevier Inc. All rights reserved.