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犬肾上腺中的毒蕈碱型胆碱能受体。

Muscarinic cholinergic receptors in canine adrenal gland.

作者信息

Tobin J R, Breslow M J, Traystman R J

机构信息

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.

出版信息

Am J Physiol. 1992 Oct;263(4 Pt 2):H1208-12. doi: 10.1152/ajpheart.1992.263.4.H1208.

Abstract

Muscarinic cholinergic receptor stimulation has been reported to modulate adrenal catecholamine and steroid secretion and influence medullary vascular tone. The present study was undertaken to localize and characterize muscarinic cholinergic receptor binding sites in canine adrenal medulla and cortex. Binding studies using semipurified membranes demonstrated specific, saturable binding of L-[benzilic-4,4'-3H(N)]-quinuclidinyl benzilate ([3H]QNB) in medulla, with a dissociation constant (KD) equal to 152 pM and estimated maximal binding sites (Bmax) equal to 179 fmol/mg protein. Displacement of [3H]QNB by cholinergic agents in order of decreasing potency was atropine, pirenzepine, oxotremorine, pilocarpine, and carbamylcholine, suggesting the receptor was M1 subtype, similar to sympathetic ganglion muscarinic receptors. Autoradiographic imaging studies demonstrated highly specific, homogeneous binding throughout the medulla. No specific binding was found in adrenal cortex. These results suggest that muscarinic effects on blood flow may be neurally mediated, rather than the result of stimulation of vascular muscarinic receptors. In medulla, muscarinic receptors are evenly distributed and modulate catecholamine secretion in all cells rather than subpopulations of cells as in other species. Absence of [3H]QNB binding in cortex argues against muscarinic receptor modulation of cortical steroid secretion.

摘要

据报道,毒蕈碱型胆碱能受体刺激可调节肾上腺儿茶酚胺和类固醇分泌,并影响髓质血管张力。本研究旨在定位和表征犬肾上腺髓质和皮质中的毒蕈碱型胆碱能受体结合位点。使用半纯化膜进行的结合研究表明,L-[苄基-4,4'-3H(N)]-喹核醇苯甲酸酯([3H]QNB)在髓质中具有特异性、可饱和结合,解离常数(KD)等于152 pM,估计最大结合位点(Bmax)等于179 fmol/mg蛋白质。胆碱能药物对[3H]QNB的置换效力由高到低依次为阿托品、哌仑西平、氧化震颤素、毛果芸香碱和氨甲酰胆碱,提示该受体为M1亚型,类似于交感神经节毒蕈碱受体。放射自显影成像研究表明,整个髓质中存在高度特异性、均匀的结合。在肾上腺皮质中未发现特异性结合。这些结果表明,毒蕈碱对血流的影响可能是神经介导的,而非血管毒蕈碱受体刺激的结果。在髓质中,毒蕈碱受体均匀分布,调节所有细胞而非其他物种中的亚群细胞分泌儿茶酚胺。皮质中缺乏[3H]QNB结合表明毒蕈碱受体对皮质类固醇分泌没有调节作用。

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