代谢型谷氨酸受体6
代谢型谷氨酸受体
代谢型谷氨酸受体4
代谢型谷氨酸受体2
代谢型谷氨酸受体7
代谢型谷氨酸受体1
代谢型谷氨酸受体5
兴奋剂
代谢受体
代谢型谷氨酸受体3
C级GPCR
代谢型谷氨酸受体8
化学
谷氨酸受体
药理学
受体
神经科学
生物化学
医学
生物
作者
Darryle D. Schoepp,Bryan G. Johnson,Rebecca A. Wright,Craig R. Salhoff,N.G. Mayne,Size Wu,Sandra L. Cockerham,J. Paul Burnett,R Belegaje,David Bleakman,James A. Monn
标识
DOI:10.1016/s0028-3908(96)00160-8
摘要
The novel compound LY354740 is a conformationally constrained analog of glutamate, which was designed for interaction at metabotropic glutamate (mGlu) receptors. In this paper the selectivity of LY354740 for recombinant human mGlu receptor subtypes expressed in non-neuronal (RGT) cells is described. At human mGlu2 receptors, LY354740 produced >90% suppression of forskolin-stimulated cAMP formation with an ec50 of 5.1 ± 0.3 nM. LY354740 was six-fold less potent in activating human mGlu3 receptors (ec50 = 24.3 ± 0.5 nM). LY354740 inhibition of forskolin-stimulated cAMP formation in human mGlu2 receptor-expressing cells was blocked by competitive mGlu receptor antagonists, including (+)-α-methyl-4-carboxyphenylglycine (MCPG) and LY307452 ((2S,4S0-2-amino-4-(4,4-diphenylbut-1-yl)-pentane-1,5-dioic acid). LY354740 had no agonist or antagonist activities at cells expressing human mGlu4 or mGlu7 (group III mGlu receptors) (ec50s > 100 000 nM). When tested at group I phosphoinositide-coupled human mGlu receptors (mGlu1a and mGlu5a), LY354740 did not activate or inhibit mGlu receptor agonist-evoked phosphoinositide hydrolysis at up to 100 000 nM. Electrophysiological experiments also demonstrated that LY354740 also had no appreciable activity in cells expressing human recombinant AMPA (GluR4) and kainate (GluR6) receptors. Thus, LY354740 is a highly potent, efficacious and selective group II (mGlu2/3) receptor agonist, useful to explore the functions of these receptors in situ. © 1997 Elsevier Science Ltd. All rights reserved.
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