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Cellular Ca mobilization and muscarinic relaxation in mammalian iris dilator muscle.

哺乳动物虹膜扩张肌中的细胞 Ca 动员和毒蕈碱松弛。

基本信息

批准号：
63571055
负责人：
WATANABE Minoru
金额：
$ 1.41万
依托单位：
Nagoya City University, Faculty of Pharmaceutical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63571055/
关键词：
iris dilator smooth muscle Ca mobilization relaxation muscarinic effect high potassium solution autonomic innervation denervation effects

项目摘要

The aim of this project is to elucidate the Ca mobilizing mechanism underlying changes in muscle tension when transmitters, autacoids and drugs are applied to iris dilator muscle of the rat and some other species. Special efforts were made to investigate the mechanisms of relaxation induced by muscarinic stimulation. First, it is found that the muscarinic relaxation is mediated by M_2-like receptor, whereas the conventional classification of muscarinic receptors into M_1 and M_2 does not fit well to characteristics of the receptor in the rat and pig iris dilator (J. Eye, 1988). Second, a striking finding was obtained that the relaxation induced not only by nerve stimulation but also by exogenously applied muscarinic agonist disappeared after parasympathectomy by ciliary ganglionectomy (E.J.P.,1988). This suggests that the muscarinic relaxation may not occur directly but mediate a release of relaxing substance from cells nearby. Therefore, substances which induce relaxation in dilator m … More uscle were widely surveyed. It was finally found that high K^+ solution induced marked relaxation when Ca, alpha- and beta- adrenergic, and muscarinic antagonists were simultaneously present (B.J.P., 1990). Since the high K^+-induced relaxation was also abolished after parasympathectomy (manuscript in preparation), an additional indirect evidence to the assumption was obtained. The relaxing substance is neither the endothelium derived relaxing factor in vascularture and probably nor a peptide. On the other hand, sympathectomy by superior ganglionectomy did not alter the muscarinic relaxation, whereas a specific increase in sensitivity to noradrenaline was observed. The supersensitivity is due to the abolishment of noradrenaline-uptake after degeneration of sympathetic nerve endings (J.J.P., 1989). Beta-adrenergic and some other relaxations were not affected by sympathectomy either (manuscript in preparation). The measurement of intracellular Ca concentration by fluorescent indicator, fura2, was considered to be one of the most effective approaches to clarify the cellular Ca mobilization, the success rate of concomitant measurements of [Ca]_i and tension was very low in the rat dilator tissue because of its small size. Sufficient results for publication have not been obtained. From the results mentioned above, it is highly possible that muscarinic agonists and high K^+ solution induce relaxation of dilator muscle via release of a relaxing substance somewhat relating to parasympathetic but not sympathetic innervation. Further study is required to determine the relaxing substance. Less

本项目旨在阐明当递质、类自身素和药物作用于大鼠及其他动物的虹膜扩张肌时，肌张力变化的钙动员机制。对毒蕈碱刺激引起松弛的机制作了特别的研究。首先，发现毒蕈碱的松弛是由M_2样受体介导的，而传统的将毒蕈碱受体分为M_1和M_2的方法并不符合大鼠和猪虹膜扩张器受体的特点（J. Eye, 1988）。其次，一个惊人的发现是，在睫状神经节切除副交感神经后，不仅由神经刺激引起的松弛，而且外源性应用毒菌碱激动剂引起的松弛也消失了（E.J.P,1988）。这表明毒蕈碱性松弛可能不是直接发生的，而是介导附近细胞释放松弛物质。因此，对引起扩张肌松弛的物质进行了广泛的研究。最后发现，当Ca， α -和β -肾上腺素能和毒蕈碱拮抗剂同时存在时，高K +溶液诱导明显的松弛（B.J.P, 1990）。由于高K^+诱导的松弛在副交感神经切除术后也被消除（手稿正在准备中），因此获得了对该假设的额外间接证据。这种松弛物质既不是血管内皮来源的松弛因子，也可能不是肽。另一方面，通过上神经节切除术进行交感神经切除术并没有改变毒瘤神经松弛，而对去甲肾上腺素的敏感性特异性增加被观察到。这种超敏感是由于交感神经末梢变性后去甲肾上腺素摄取的消除（J.J.P, 1989）。-肾上腺素能和其他一些松弛也不受交感神经切除术的影响（手稿准备中）。荧光指示剂fura2测量细胞内Ca浓度被认为是明确细胞内Ca动员的最有效方法之一，但由于大鼠扩张组织体积小，同时测量[Ca]_i和张力的成功率很低。尚未获得足够的结果发表。从上述结果来看，毒蕈碱激动剂和高K^+溶液极有可能通过释放一种与副交感神经有关但与交感神经无关的放松物质来诱导扩张肌的松弛。需要进一步的研究来确定松弛物质。少