钾离子通道开放剂可激活大脑中磺酰脲类敏感的钾离子通道，并阻断神经分泌。
K+ channel openers activate brain sulfonylurea-sensitive K+ channels and block neurosecretion.
作者信息
Schmid-Antomarchi H, Amoroso S, Fosset M, Lazdunski M
机构信息
Institut de Pharmacologie Moléculaire et Cellulaire, UPR 411 Centre National de la Recherche Scientifique, Valbonne, France.
出版信息
Proc Natl Acad Sci U S A. 1990 May;87(9):3489-92. doi: 10.1073/pnas.87.9.3489.
Abstract
Vascular K+ channel openers such as cromakalim, nicorandil, and pinacidil potently stimulate 86Rb+ efflux from slices of substantia nigra. This 86Rb+ efflux is blocked by antidiabetic sulfonylureas, which are known to be potent and specific blockers of ATP-regulated K+ channels in pancreatic beta cells, cardiac cells, and smooth muscle cells. K0.5, the half-maximal effect of the enantiomer (-)-cromakalim, is as low as 10 nM, whereas K0.5 for nicorandil is 100 nM. These two compounds appear to have a much higher affinity for nerve cells than for smooth muscle cells. Openers of sulfonylurea-sensitive K+ channels lead to inhibition of gamma-aminobutyric acid release. There is an excellent relationship between potency to activate 86Rb+ efflux and potency to inhibit neurotransmitter release.
摘要
血管钾通道开放剂，如克罗卡林、尼可地尔和平尼地尔，能有效刺激黑质切片中的86Rb+外流。这种86Rb+外流可被抗糖尿病磺脲类药物阻断，已知这些药物是胰腺β细胞、心肌细胞和平滑肌细胞中ATP调节钾通道的强效特异性阻断剂。对映体（-）-克罗卡林的半数最大效应浓度（K0.5）低至10 nM，而尼可地尔的K0.5为100 nM。这两种化合物对神经细胞的亲和力似乎比对平滑肌细胞高得多。磺脲类敏感钾通道开放剂会导致γ-氨基丁酸释放受到抑制。激活86Rb+外流的效力与抑制神经递质释放的效力之间存在良好的相关性。
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Proc Natl Acad Sci U S A. 1990 May;87(9):3489-92. doi: 10.1073/pnas.87.9.3489.
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本文引用的文献
1
Alkaloids of neotropical poison frogs (Dendrobatidae).
Fortschr Chem Org Naturst. 1982;41:205-340. doi: 10.1007/978-3-7091-8656-5_6.
2
Specific receptors for sulfonylureas in brain and in a beta-cell tumor of the rat.大鼠脑及胰岛β细胞瘤中磺脲类药物的特异性受体。
Biochem Pharmacol. 1982 Mar 15;31(6):1171-4. doi: 10.1016/0006-2952(82)90363-x.
3
The effect of veratridine on excitable membranes of nerve and muscle.藜芦碱对神经和肌肉可兴奋膜的作用。
Ergeb Physiol. 1969;61:18-71. doi: 10.1007/BFb0111446.
4
Inhibition of 3H-glibenclamide binding to sulfonylurea receptors by oral antidiabetics.
Arzneimittelforschung. 1985;35(4):707-12.
5
D-[3H]aspartate release from hippocampus slices studied in a multiwell system: controlling factors and postnatal development of release.
Brain Res. 1987 Feb 3;402(2):255-63. doi: 10.1016/0006-8993(87)90031-x.
6
Actions of BRL 34915 (Cromakalim) upon convulsive discharges in guinea pig hippocampal slices.BRL 34915（克罗卡林）对豚鼠海马切片惊厥性放电的作用。
Naunyn Schmiedebergs Arch Pharmacol. 1988 Apr;337(4):429-34. doi: 10.1007/BF00169535.
7
Mechanism of action of minoxidil sulfate-induced vasodilation: a role for increased K+ permeability.硫酸米诺地尔诱导血管舒张的作用机制：钾离子通透性增加的作用。
J Pharmacol Exp Ther. 1988 Jun;245(3):751-60.
8
Characterization, purification, and affinity labeling of the brain [3H]glibenclamide-binding protein, a putative neuronal ATP-regulated K+ channel.脑[3H]格列本脲结合蛋白的特性鉴定、纯化及亲和标记，一种假定的神经元ATP调节钾通道
Proc Natl Acad Sci U S A. 1988 Dec;85(24):9816-20. doi: 10.1073/pnas.85.24.9816.
9
Effect of the K+ efflux stimulating vasodilator BRL 34915 on 86Rb+ efflux and spontaneous activity in guinea-pig portal vein.钾离子外流刺激血管扩张剂BRL 34915对豚鼠门静脉86Rb+外流及自发活动的影响
Br J Pharmacol. 1987 Jul;91(3):569-78. doi: 10.1111/j.1476-5381.1987.tb11250.x.
10
Electrophysiologic effects of nicorandil, a new antianginal agent, on action potentials and membrane currents of rabbit atrioventricular node.新型抗心绞痛药物尼可地尔对兔房室结动作电位和膜电流的电生理效应
Naunyn Schmiedebergs Arch Pharmacol. 1987 May;335(5):567-74. doi: 10.1007/BF00169126.
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