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

本项目的目的是阐明递质、金刚类化合物和药物应用于大鼠虹膜扩张肌和其他物种时，肌张力变化背后的钙动员机制。我们特别研究了毒扁豆碱刺激引起的松弛机制。首先，我们发现M_2受体介导了M_2受体的松弛，而传统的M_1和M_2受体分类不能很好地适应大鼠和猪虹膜扩张器M_2受体的特点(J.Eye，1988)。第二，发现睫状神经节切除副交感神经后，不仅神经刺激引起的松弛消失，外源性M受体激动剂引起的松弛也消失了(E.J.P.，1988)。这表明毒鼠碱的松弛可能不是直接发生的，而是介导了附近细胞的松弛物质的释放。因此，导致扩张器m…松弛的物质更多的人接受了广泛的调查。最后发现，当钙、α-和β-肾上腺素能以及M受体拮抗剂同时存在时，高K~(++)溶液可引起显著的松弛(B.J.P.，1990)。由于高K^+诱导的松弛在副交感神经切除后也被取消(手稿正在准备中)，因此获得了支持这一假设的额外的间接证据。这种松弛物质既不是血管内皮衍生的松弛因子，也可能不是一种多肽。另一方面，通过上神经节切除交感神经并不改变毒碱的松弛，而对去甲肾上腺素的敏感性有明显的增加。这种超敏反应是由于交感神经末梢变性后去甲肾上腺素摄取的取消(J.P.，)。交感神经切除也不影响β-肾上腺素能和其他一些松弛(手稿正在准备中)。用荧光指示剂FURA2测量细胞内钙离子浓度被认为是阐明细胞内钙离子动员的最有效方法之一，但同时测量[Ca]i和张力的成功率很低，因为它的体积小。尚未获得足够的结果以供发表。上述结果表明，毒扁豆碱激动剂和高K~+溶液很可能通过释放一种与副交感神经支配而非交感神经支配有关的松弛物质来引起扩张肌的松弛。需要进一步研究才能确定松弛物质。较少

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