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

众所周知，肾上腺染色质细胞具有毒蕈碱受体和烟碱受体，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，而是从一些细胞内储存部位动员Ca^<2+>的结果。本实验主要研究：(1)毒蕈碱受体与烟碱受体相互作用导致儿茶酚胺分泌的模式；(2)细胞内与毒蕈碱受体相关的Ca^<2+>储存的性质；(3)该假设储存释放Ca^<2+>的机制。为此，我们使用灌注的猫和豚鼠肾上腺，分离的狗和豚鼠肾上腺染色质细胞和培养的牛肾上腺染色质细胞。研究结果总结如下：1。由烟碱（5xlO^<-5>M）引起的儿茶酚胺分泌明显增加，更早地应用纯毒蕈碱激动剂氧tremorine (10^<-5>M)，其本身仅引起一分钟的分泌反应。因此，当乙酰胆碱从肾上腺染色质细胞释放儿茶酚胺时，烟碱受体和毒蕈碱受体似乎相互作用。肾上腺染色质细胞似乎至少拥有两种不同的Ca^<2+>储存，负责平滑肌细胞中儿茶酚胺的分泌。一种对咖啡因敏感，另一种对毒蕈碱受体的激活敏感，其第二信使已知是IP_3。这两家商店似乎有部分重叠。与平滑肌细胞相似，咖啡因敏感的储存被ryanodine锁定在开放状态。这些结果表明Ca^<2+>诱导的Ca^<2+>释放机制存在于肌肉细胞中。证实了咖啡因和乙酰胆碱可引起载Fura 2- am的培养牛肾上腺嗜铬细胞胞质游离Ca^<2+>浓度升高。Ryanodine选择性阻断咖啡因诱导的Ca^<2+>浓度的升高。少

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