CHARACTERISTIC OF INTRACELLULAR CALCIUM STORES RESPONSIBLE FOR CATECHOLAMINE SECRETION IN ADRENAL MEDULLARY CHROMAFFIN CELLS

肾上腺髓质嗜铬细胞胞内钙储存负责儿茶酚胺分泌的特征

• 批准号: 03454103
• 负责人: NAKAZATO Yoshikazu
• 金额: $ 3.71万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454103/
• 关键词: Ca^<2+> store; Ca^<2+>-induced Ca^<2+> release; Caffeine; Catecholamine; Whole cell patch clamp; Nicotinic currents; Fure 2; Concentration of intracellular Ca^<2+>; ^<45>Ca^<2+>; 小胞体; 分泌顆粒; 電位依存性イオンチャネル; 潅流副腎; カテコ-ルアミン; 副腎随質培養細胞; ムスカリン受溶体刺激

We have found that unlike catecholamine secretion induced by nicotinic receptor activation, the secretory response to muscarinic receptor stimulation is not simply resulting from increase in Ca^<2+> influx,but from mobilization of intracellulary stored Ca^<2+> in cat adrenal glands (Nakazato et al.,1984). Since the same was true in guinea-pig adrenal glands, Ca^<2+> stores linked to muscarinic receptor have been suggested to be present in the adrenal chromaffin cells, regardless of the species. In this research project, first, the possibility of the presence of Ca^<2+> stores other than those linked to muscarinic receptors was determined by using caffeine which has been known to initiate Ca^<2+>-induced Ca^<2+> release from sarcoplamic reticulum of the muscle. Secondly, the ability of subcellular organella to accumulate ^<45>Ca^<2+> was studied to specify the candidate for Ca^<2+> store, thirdly the effect of caffeine on Ca^<2+> mobilization or catecholamine secretion induced by acetyl … More choline and finally, the effect on membrane currents under the condition of whole cell patch clamp were investigated. The results are summarized in the following; (1) caffeine caused a marked increase in catecholamine secretion from adrenal chromaffin cells of cat, guinea-pig and ox, (2) the effectiveness of caffeine was depressed by the presence of extracellular Ca^<2+>, Mg^<2+> and/or Na^+, (3) ryanodine blocked the secretory response to caffeine, but partially inhibited the response to muscarinic stimulation. (4) Both endoplasmic reticulum and secretory granules had the capacity to accumulate ^<45>Ca^<2+> in a similar extent. (5) Caffeine inhibited catecholamine secretion induced by acetylcholine, high K^+ and veratridine. (6) Acetylcholine initiated nicotinic receptor current and depolarization evoked voltage-dependent Na^+, K^+ and Ca^<2+> in chromaffin cells and (7) all of these currents were inhibited by caffeine. These results suggest that the ineffectiveness of caffeine in releasing catecholamine in the presence of extracellular Ca^<2+> and/or Na^+ is due to the inhibitory action of caffeine itself on both receptor linked and volgate- dependent ionic channels. Less

我们发现，与烟碱受体激活诱导的儿茶酚胺分泌不同，对毒蕈碱受体刺激的分泌反应并非简单地由Ca^2+流入的增加引起，而是由猫肾上腺中细胞内储存的Ca^2+的动员引起(Nakazato等，1984)。由于在豚鼠肾上腺中也是如此，因此与毒蕈碱受体相关的Ca 2+ 储存被认为存在于肾上腺嗜铬细胞中，而与物种无关。在该研究项目中，首先，通过使用咖啡因来确定除与毒蕈碱受体相关的那些以外的Ca^<2+>储存的存在的可能性，已知咖啡因会引发Ca^<2+>诱导的Ca^<2+>从肌肉的肌浆网释放。其次，研究了亚细胞细胞器积累^<45>Ca^<2+>的能力，以确定Ca^<2+>储存的候选者；再次，研究了咖啡因对乙酰胆碱诱导的Ca^<2+>动员或儿茶酚胺分泌的影响；最后，研究了全细胞膜片钳条件下对膜电流的影响。结果总结如下： (1) 咖啡因导致猫、豚鼠和牛的肾上腺嗜铬细胞的儿茶酚胺分泌显着增加，(2) 咖啡因的有效性因细胞外 Ca^2+、Mg^2+ 和/或 Na^+ 的存在而降低，(3) 兰尼碱阻断对咖啡因的分泌反应，但部分抑制对毒蕈碱的反应 刺激。 (4)内质网和分泌颗粒都具有相似程度的积累^ 45 Ca ^ 2+ 的能力。 (5)咖啡因抑制乙酰胆碱、高K^+和藜芦碱诱导的儿茶酚胺分泌。 (6)乙酰胆碱引发烟碱受体电流和去极化在嗜铬细胞中引起电压依赖性Na + 、K + 和Ca + 2+ ，并且(7)所有这些电流都被咖啡因抑制。这些结果表明，在细胞外Ca 2+ 和/或Na 2+ 存在的情况下，咖啡因在释放儿茶酚胺方面无效是由于咖啡因本身对受体连接和伏尔加特依赖性离子通道的抑制作用。较少的

项目成果

NAKAZATO, Y.: "INHIBITORY EFFECTS OF CAFFEINE ON AGONIST-INDUCED CATECHOLAMINE SECRETION FROM ADRENAL CHROMAFFIN CELLS" 7TH INTERNATIONAL CATECHOLAMINE SYMPOSIUM, ABSTRACTS. 228 (1992)

Nakazato, Y.：“咖啡因对肾上腺嗜铬细胞激动剂诱导的儿茶酚胺分泌的抑制作用”，第七届国际儿茶酚胺研讨会，摘要。

Yoshikazu Nakazato;Hirotaka Hayashi;Hiroki Teraoka: "Comparisons of the effects of ryanodine on catecholamine secretion evoked by caffeine and acetylcholine in perfused adrenal glands of the guineaーpig" British Journal of Pharmacology. 105. 597-602 (1992)

Yoshikazu Nakazato；Hirotaka Hayashi；Hiroki Teraoka：“兰尼碱对豚鼠肾上腺灌注中咖啡因和乙酰胆碱引起的儿茶酚胺分泌的影响的比较”英国药理学杂志 105. 597-602 (1992)。

NAKAZATO,Y.: "COMRARISONS OF THE EFFECT OF RYANODINE ON CATECHOLAMINE SECRETION EVOKED BY CAFFEINE AND ACETYLCHOLINE IN PERFUSED ADRENAL GLANDS OF GUINEA-PIG" BR.J.PHARMACOL. 105. 597-802 (1992)

Nakazato,Y.：“在豚鼠肾上腺灌注中，兰尼定对咖啡因和乙酰胆碱引起的儿茶酚胺分泌的影响的比较” BR.J.PHARMACOL。

SATOH, E.: "EFFECTS OF MONENSIN AND VERATRIDINE ON ACETYLCHOLINE RELEASE AND CYTOSOLIC FREE Ca^<2+> LEVELS IN CEREBROCORTICAL SYNAPTOSOMES OF RATS" J. NEUROCHEM.57. 1270-1275 (1991)

SATOH, E.：“莫能菌素和藜芦定对大鼠大脑皮质突触体中乙酰胆碱释放和胞质游离 Ca^<2> 水平的影响”J. NEUROCHEM.57。

TERAOKA,H.: "RYANODINE INHIBITS CAFFEINE-EVOKED Ca^<2+> MOBILIZATION AND CATECHOLAMINE SECRETION FROM CULTURED BOVINE ADRENAL CHROMAFFIN CELLS" J.NEURPCHEM. 57. 1884-1890 (1991)

TERAOKA,H.：“RYANODINE 抑制咖啡因诱发的 Ca^2 > 动员和培养的牛肾上腺嗜铬细胞的儿茶酚胺分泌”J.NEURPCHEM。