INTERACTION BETWEEN MUSCARINIC AND NICOTINIC RECEPTORS IN CATECHOLAMINE SECRETION FROM ADRENAL MEDULLARY CELLS

肾上腺髓质细胞分泌儿茶酚胺中毒蕈碱和烟碱受体之间的相互作用

• 批准号: 63480085
• 负责人: NAKAZATO Yoshikazu
• 金额: $ 4.22万
• 依托单位: OBIHIRO UNIVERSITY OF AGRICULTURE AND VETERINARY MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 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/en/grant/KAKENHI-PROJECT-63480085/
• 关键词: Adrenal chromaffin cells; Muscarinic receptor; Nicotinic receptor; Cytosolic free Ca^<2+>; Caffeine; Ryanodine; ライアノジン; Fura2-AM; ムスカリ-ン受容体; カキコルアミン; 細胞内カルシウム; ニコチン受容体; 副腎髄質

It is well known that adrenal chromaffin cells possess both muscarinic and nicotinic receptors involved in acetylcholine-induced catecholamine secretion.We have found that unlike catecholamine secretion induced by nicotinic receptor activation, muscarinic receptor-mediated secretory response was not a result of increased Ca^<2+> influx, but of mobilized Ca^<2+> from some intracellular storage sites. In this experiment, the study was made about, (1) the mode of interaction between muscarinic and nicotinic receptors in causing catecholamine secretion, (2) the nature of intracellular Ca^<2+> store linked to muscarinic receptors and (3) Ca^<2+> releasing mechanism from that hypothetical store. For this purpose, we used perfused adrenal glands of cat and guinea pig, isolated adrenal chromaffin cells of dog and guinea pig and cultured bovine adrenal chromaffin cells. The results are summarized as follows: 1. Catecholamine secretion evoked by nicotine (5xlO^<-5>M) was markedly increased by pr … More eceding application of a pure muscarinic agonist, oxotremorine (10^<-5>M) which caused only a minute secretory response by itself. It appears therefore that both nicotinic and muscarinic receptors interact with each other when acetylcholine releases catecholamine from adrenal chromaffin cells.2. Adrenal chromaffin cells seem to possess at least two different Ca^<2+> stores responsible for catecholamine secretion as suggested in smooth muscle cells.One is sensitive to caffeine and the other one is to muscarinic receptor activation of which the second messenger is known to be IP_3. There appears to be a partial overlap in both stores. Similar to that of smooth muscle cells, caffeine-sensitive stores are suggested to be locked by ryanodine in open state. These results suggest that Ca^<2+>-induced Ca^<2+> release mechanism is present as it is in muscle cells.3. It was confirmed that caffeine and acetylcholine cause increase in cytosolic free Ca^<2+> concentration in cultured bovine adrenal chromaffin cells loaded with Fura 2-AM. Ryanodine selectively blocked the caffeine-induced Increase in the Ca^<2+> concentration. Less

众所周知，肾上腺嗜铬细胞同时具有毒蕈碱和烟碱受体，参与乙酰胆碱诱导的儿茶酚胺分泌，我们发现，与烟碱受体激活诱导的儿茶酚胺分泌不同，毒蕈碱受体介导的分泌反应不是Ca^2+内流增加的结果，而是从细胞内某些储存位点动员Ca^2+的结果。在这个实验中，我们研究了：（1）毒蕈碱型受体和烟碱型受体在引起儿茶酚胺分泌中的相互作用方式;（2）与毒蕈碱型受体相关的细胞内Ca^2+库的性质;（3）Ca^2+从这种假设的钙库中释放的机制。为此，我们用猫和豚鼠的肾上腺灌流，分离的狗和豚鼠的肾上腺嗜铬细胞和培养的牛肾上腺嗜铬细胞。主要研究结果如下：1.尼古丁（5 × 10 ^ M）诱发的儿茶酚胺分泌<-5>， ...更多信息 停止应用纯的毒蕈碱激动剂，氧化震颤素（10 μ <-5>M），其本身仅引起微小的分泌反应。因此，当乙酰胆碱从肾上腺嗜铬细胞释放儿茶酚胺时，烟碱和毒蕈碱受体似乎相互作用。肾上腺嗜铬细胞似乎至少有两种不同的Ca^&lt;2+&gt;库，一种对咖啡因敏感，另一种对毒蕈碱受体（已知其第二信使是IP_3）的激活敏感，这两种Ca ^&lt;2+库与平滑肌细胞中的儿茶酚胺分泌有关。两个商店似乎有部分重叠。与平滑肌细胞相似，咖啡因敏感的储存库被ryanodine锁定在开放状态。这些结果表明，Ca^&lt;2+&gt;诱导的Ca^&lt;2+&gt;释放机制在肌细胞中同样存在.结果表明，咖啡因和乙酰胆碱可引起Fura 2-AM负载的牛肾上腺嗜铬细胞胞浆游离Ca^2+浓度升高。Ryanodine选择性地阻断咖啡因诱导的Ca^&lt;2+&gt;浓度升高。少

项目成果

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TERAOKA, H.: "THE ROLE OF Na^+ IN MUSCARINIC RECEPTOR-MEDIATED CATECHOLAMINE SECRETION IN THE ABSENCE OF EXTRACELLULAR Ca^<2+> IN PERFUSED CAT ADRENAL GLANDS" BR. J. PHARMACOL., 1990.

TERAOKA, H.：“在灌注猫肾上腺中，在缺乏细胞外 Ca ^ 2 > 的情况下，Na ^ 在毒蕈碱受体介导的儿茶酚胺分泌中的作用” BR。

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SATOH, E.: "[^3H]ACETYLCHOLINE RELEASE AND THE CHANGE IN CYTOSOLIC FREE CALCIUM LEVEL INDUCED BY HIGH K^+ AND OUABAIN IN RAT BRAIN SYNAPTOSOMES" NEUROSCI. LETT., 107, 1989, 284-288.

SATOH, E.：“大鼠脑突触体中高 K^ 和哇巴因引起的[^3H]乙酰胆碱释放和胞浆游离钙水平的变化”NEUROSSCI。

NAKAZATO, Y.: "EFFECTS OF MUSCARINIC PHARMACOPHORES ON THE CHOLINERGIC REGULATION OF CATECHOLAMINE SECRETION FROM PERFUSED ADRENAL GLANDS" ARCH. INT. PHARMACODYN., 293, 1988, 209-218.

Nakazato，Y.：“毒蕈碱药效团对灌注肾上腺儿茶酚胺分泌的胆碱能调节的影响”。