Neurohormonal receptors and cyclic AMP-binding proteins in rabbit tracheal mucosa-submucosa.
Neurohormonal receptors and cyclic AMP-binding proteins in rabbit tracheal mucosa-submucosa.
复制标题
兔气管粘膜-粘膜下层中的神经激素受体和环AMP结合蛋白。
DOI：
10.1016/0304-4165(82)90086-1
复制
发表时间：
1982
期刊：
影响因子：
--
通讯作者：
S. A. Rudolph
中科院分区：
文献类型：
--
作者：
C. Liedtke;T. Boat;S. A. Rudolph
检查了改变体外气管电解质转运和粘液糖蛋白分泌的神经激素和药物改变兔气管粘膜-粘膜下层的无平滑肌制剂中环核苷酸积累的能力。 β-肾上腺素能激动剂、组胺、2-Cl-腺苷和前列腺素 E1 会增加 cAMP 水平。卡巴胆碱增加了 cGMP 水平。磷酸二酯酶抑制剂异丁基甲基黄嘌呤可增加 cAMP 和 cGMP 水平，并且仅增强 β-肾上腺素能作用。 β-肾上腺素能作用被(±)-普萘洛尔阻断，组胺作用被苯海拉明、阿托品和(±)-普萘洛尔阻断。阿托品阻断了卡巴胆碱的作用。与粘膜-粘膜下层相比，兔气管分离的表面上皮具有更高的基础cAMP水平，并且对β-肾上腺素能激动剂和异丁基甲基黄嘌呤的反应更大。气管粘膜-粘膜下层中的两种主要 cAMP 结合蛋白通过光亲和标记 8-N3-[32P]cAMP 进行鉴定。增加 cAMP 水平的药物也会降低光亲和标记，表明这两种 cAMP 结合蛋白被完整细胞占据。蛋白质的分子量分别为 50 000 和 54 000，其电泳迁移率分别对应于 I 型和 II 型 cAMP 依赖性蛋白激酶的调节亚基。结果与气道上皮功能受到多种增加环核苷酸水平的激动剂调节的假设一致。 β-肾上腺素能激动剂的作用显然是由腺苷酸环化酶的激活和随后的 cAMP 依赖性蛋白激酶的激活介导的。
Neurohormones and drugs that alter in vitro tracheal electrolyte transport and mucus glycoprotein secretion were examined for their ability to alter cyclic nucleotide accumulation in a smooth muscle-free preparation of rabbit tracheal mucosa-submucosa. cAMP levels were increased by β-adrenergic agonists, histamine, 2-Cl-adenosine and prostaglandin E1. cGMP levels were increased by carbachol. The phosphodiesterase inhibitor isobutylmethylxanthine increased cAMP and cGMP levels and potentiated only the β-adrenergic effects. The β-adrenergic effects were blocked by (±)-propranolol and the effects of histamine by diphenhydramine, atropine and (±)-propranolol. Atropine blocked the carbachol effects. The isolated surface epithelium from rabbit trachea had higher basal cAMP levels and greater response to β-adrenergic agonists and isobutylmethylxanthine than the mucosa-submucosa. Two major cAMP-binding proteins in the tracheal mucosa-submucosa were identified with the photoaffinity label 8-N3-[32P]cAMP. Agents that increased cAMP levels also decreased photoaffinity labelling, suggesting that these two cAMP-binding proteins were being occupied in the intact cell. The molecular weights of the proteins were 50 000 and 54 000 and correspond in electrophoretic mobility to the regulatory subunits of Type-I and Type-II cAMP-dependent protein kinases, respectively. The results are consistent with the hypothesis that epithelial functions in the airways are modulated by a number of agonists which increase cyclic nucleotide levels. The effects of β-adrenergic agonists is apparently mediated by activation of adenylate cyclase and subsequent activation of cAMP-dependent protein kinases.