Comparative analysis of nitric oxide and SALMFamide neuropeptides as general muscle relaxants in starfish
Comparative analysis of nitric oxide and SALMFamide neuropeptides as general muscle relaxants in starfish
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DOI：
10.1242/jeb.00197
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发表时间：
2003-03-01
影响因子：
2.8
通讯作者：
Elphick, MR
中科院分区：
文献类型：
--
作者：
Melarange, R;Elphick, MR
先前的研究已经确定，气体信号分子一氧化氮（NO）和SALMF酰胺神经肽S1和S2引起海星红海星的心脏胃舒张。在这里，我们表明，S1，S2和NO供体SNAP也引起松弛的其他两个准备从Asterias -管脚和顶肌的体壁。当浓度为10 μ mol l（-1）时，作为肌肉松弛剂的有效性的等级顺序为SNAP>S2>S1，对于管足和顶肌，而对于贲门胃，则为S2>S1>SNAP。值得注意的是，这些数据表明NO和SALMFamide神经肽在海星中起一般肌肉松弛剂的作用，但它们在不同器官系统中的相对重要性不同。NO和SALMFamide引起海星肌肉松弛的分子机制尚不清楚，但先前使用可溶性鸟苷酸环化酶抑制剂1H-[1，2，4]恶二唑[4，3-a]喹喔啉-1-酮（ODQ）表明，环核苷酸第二信使cGMP可能介导NO的作用。与此假设一致，在这里，我们报告ODQ也导致部分抑制SNAP对管足和心尖肌的松弛作用。为了进一步研究作为介体的NO和SALMFamides对海星肌肉的影响的环核苷酸的参与，我们已经测量了cGMP和cAMP在心脏胃和心尖肌用S1，S2或SNAP处理后。然而，与对照组相比，未观察到环核苷酸含量的显著变化。在环核苷酸磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤（IBMX）的存在下，对顶端肌肉组织进行了进一步的实验，IBMX是一种也会导致海星心脏胃松弛的药物。用IBMX处理导致cGMP和cAMP的基础水平增加2-3倍，但用IBMX和S1或S2或SNAP共同处理导致没有显著进一步增加到单独用IBMX观察到的水平以上。从这些数据中，我们得出结论，NO对海星肌肉的松弛作用可能是由cGMP依赖性和cGMP非依赖性途径介导的。然而，SALMFamides引起海星肌肉松弛的机制仍然未知，尽管我们的结果不排除cGMP或cAMP的参与，但现在可能需要研究其他信号通路。
Previous studies have established that the gaseous signalling molecule nitric oxide (NO) and the SALMFamide neuropeptides S1 and S2 cause cardiac stomach relaxation in the starfish Asterias rubens. Here we show that S1, S2 and the NO donor SNAP also cause relaxation of two other preparations from Asterias - tube feet and the apical muscle of the body wall. The rank order of effectiveness as muscle relaxants when tested at a concentration of 10 mumol l(-1) was SNAP>S2>S1 for both tube feet and apical muscle whereas for cardiac stomach it was S2>S1>SNAP. Significantly, these data indicate that NO and SALMFamide neuropeptides function as general muscle relaxants in starfish but vary in their relative importance in different organ systems.The molecular mechanisms by which NO and SALMFamides cause muscle relaxation in starfish are not known, but previous pharmacological studies on the cardiac stomach using the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazol[4,3-a]quinoxalin-1-one (ODQ) indicate that the cyclic nucleotide second messenger cGMP may mediate effects of NO. Consistent with this hypothesis, here we report that ODQ also causes partial inhibition of the relaxing effect of SNAP on tube foot and apical muscle preparations. To further investigate the involvement of cyclic nucleotides as mediators of the effects of NO and SALMFamides on starfish muscle, we have measured both cGMP and cAMP in cardiac stomach and in apical muscle after treatment with S1, S2 or SNAP. However, no significant changes in cyclic nucleotide content were observed compared with controls. Further experiments were performed on apical muscle tissue in the presence of the cyclic-nucleotide-phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), a drug that also causes cardiac stomach relaxation in starfish. Treatment with IBMX caused a 2-3-fold increase above basal levels for cGMP and cAMP, but co-treatment with IBMX and S1 or S2 or SNAP resulted in no significant further increase above the level observed with IBMX alone. We conclude from these data that the relaxing action of NO on starfish muscle may be mediated by both cGMP-dependent and cGMP-independent pathways. However, the mechanisms by which SALMFamides cause muscle relaxation in starfish remain unknown and, although our results do not rule out the involvement of cGMP or cAMP, other signalling pathways may now need to be investigated.