Two distinct inhibitory actions of steroids on cholinoceptor-mediated secretion of catecholamine from guinea-pig adrenal medullary cells

Two distinct inhibitory actions of steroids on cholinoceptor-mediated secretion of catecholamine from guinea-pig adrenal medullary cells
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DOI:
10.1016/s0304-3940(02)01313-7
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发表时间:
2003-02
影响因子:
2.5
通讯作者:
K. Yonekubo;T. Ohta;S. Ito
K. Yonekubo;T. Ohta;S. Ito
中科院分区:
医学4区
文献类型:
--
作者:
K. Yonekubo;T. Ohta;S. Ito

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我们研究了地塞米松、皮质醇和醛固酮对豚鼠离体肾上腺髓质细胞对尼古丁和毒蕈碱反应的影响。尼古丁诱导的内向电流可逆地抑制这些类固醇的剂量依赖性和非竞争性的方式。这些类固醇抑制[Ca ~(2+)] i增加响应尼古丁,但不是毒蕈碱。毒蕈碱诱导的儿茶酚胺分泌被皮质醇和醛固酮抑制,但地塞米松不抑制。蛋白激酶C激活剂佛波醇12-肉豆蔻酸酯13-乙酸酯可引起儿茶酚胺分泌,皮质醇和醛固酮可抑制儿茶酚胺分泌,但地塞米松不抑制。这些结果表明,胆碱能受体刺激引起的儿茶酚胺分泌抑制类固醇通过两个不同的机制,一个是抑制烟碱受体,另一个是抑制蛋白激酶C激活在豚鼠肾上腺髓质细胞。
We investigated the effects of dexamethasone, cortisol and aldosterone on responses to nicotine and muscarine in guinea-pig isolated adrenal medullary cells. Nicotine-induced inward currents were reversibly inhibited by these steroids in a dose-dependent and non-competitive manner. These steroids inhibited an increase in [Ca2+]iin response to nicotine but not muscarine. Muscarine-induced catecholamine secretion was inhibited by cortisol and aldosterone but not dexamethasone. Phorbol 12-myristate 13-acetate, a protein kinase C activator, caused catecholamine secretion which was inhibited by cortisol and aldosterone but not dexamethasone. These results suggest that catecholamine secretion induced by cholinoceptor stimulation is inhibited by steroids via two distinct mechanisms; one is the inhibition of nicotinic receptors, another is the inhibition of protein kinase C activation in guinea-pig adrenal medullary cells.