Ontogenesis of physiological responsiveness and guanine nucleotide sensitivity of cardiac muscarinic receptors during chick embryonic development.
Ontogenesis of physiological responsiveness and guanine nucleotide sensitivity of cardiac muscarinic receptors during chick embryonic development.
复制标题
鸡胚胎发育过程中心肌毒蕈碱受体的生理反应性和鸟嘌呤核苷酸敏感性的个体发生。
DOI：
10.1021/bi00319a021
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发表时间：
1984
期刊：
影响因子：
2.9
通讯作者：
Nathanson,NM
中科院分区：
文献类型：
--
作者：
Halvorsen,SW;Nathanson,NM
Stanley W. Halvorsen 和 Neil M. Nathanson* 摘要：与 5 或 8 日胚胎的心房相比，从 4 日龄鸡胚分离的心房对毒蕈碱激动剂的负变时作用的反应要小得多，尽管所有这些年龄段的毒蕈碱乙酰胆碱受体 (mAChR) 的密度相似。 4 天胚胎心脏中的 mAChR 也明显不易受体内激动剂治疗对受体数量调节的影响，并且需要 2-5 倍剂量的毒蕈碱激动剂卡巴胆碱才能实现与 5 或 8 天胚胎心脏中观察到的受体数量减少相当的效果。当在生理缓冲液中测定 4 天心房膜时，除非存在巯基还原剂，否则激动剂与 mAChR 的结合不受 GTP 的调节。来自 5 天和 8 天胚胎的受体不需要添加巯基还原剂来观察鸟嘌呤核苷酸对激动剂结合的影响。即使存在巯基还原剂，4 天膜中与 mAChR 结合的卡巴胆碱对 5'-基亚胺二磷酸鸟苷的敏感性也低得多。乙酰胆碱从心脏的副交感神经末梢释放，并与心肌膜上的毒蕈碱乙酰胆碱受体 (s)(mAChR) 1 结合，导致收缩速率和收缩力降低。 mAChR 介导的心房窦房结起搏器放电速率减慢是由于向外 K+ 电流增加所致 (Hutter, 1957)，也可能受到缓慢向内 Ca2+/Na+ 电流减少的影响，与 K+ 电导的影响无关 (Giles & Noble, 1976)。然而，没有直接证据表明 mAChR 本身具有离子载体的功能，并且 mAChR 激活与这些生理效应耦合的分子机制仍不清楚。
Stanley W. Halvorsen and Neil M. Nathanson* abstract: Atria isolated from 4-day chick embryos were much less responsive to the negativechronotropic effect of muscarinic agonists than were atria from 5-or 8-day embryos, even though the density of muscarinic acetylcholine receptors (mAChR) was similar at all these ages. The mAChR in hearts from 4-dayembryos were also significantly less susceptible to regulation of receptor number by in vivo agonist treatment and required a 2-5-fold greater dose of the muscarinic agonist carbachol to achieve a decrease in receptor number equivalent to that observed in 5-or 8-day embryonic hearts. When 4-day atrial membranes were assayed in physiological buffers, agonist binding to the mAChR was not regulated by GTP unless a sulfhydryl reducingagent was present. Receptors from 5-and 8-day embryos did not require addition of a sulfhydryl reducing agent in order to see guanine nucleotide effects on agonist binding. Even in the presence of a sulfhydryl reducing agent, carbachol binding to the mAChR in 4-day membranes was much less sensitive to guanyl-5'-yl imidodiphosphateAcetylcholine is released from parasympathetic nerve endings in theheart and upon binding to the muscarinic acetylcholine receptor (s)(mAChR) 1 on the cardiac muscle mem-brane results in a decrease in the rate and force of contraction. mAChR-mediated slowing of the pacemaker firing rate in the sinus node of the atrium is due to an increased outward K+ current (Hutter, 1957) and may also be influenced by a de-creased slow inward Ca2+/Na+ current independent of effects on K+ conductance (Giles & Noble, 1976). However, there is no direct evidence that the mAChR itself functions as an ionophore, and the molecular mechanisms responsible for the coupling of mAChR activation to these physiological effects remain unclear.