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主页蛋白表达β-肾上腺素能受体

β-肾上腺素能受体

β-肾上腺素能受体广泛分布于中枢和外周部位,可被交感神经末梢释放的去甲肾上腺素或肾上腺髓质释放的肾上腺素(E4250, E4375)激活。β-肾上腺素能受体激活产生的重要生理学后果包括心率上升和心肌收缩力增强,血管、泌尿生殖器和支气管平滑肌松弛,刺激肾小球旁器分泌肾素,刺激内分泌胰腺分泌胰岛素和胰高血糖素,刺激肝脏和骨骼肌中的糖原分解以及刺激脂肪细胞中的脂肪分解。接头前β-肾上腺素能受体存在于一些中枢和外周神经末梢上,它们的激活会促进刺激诱发性神经递质的释放。然而,与接头前α2-肾上腺素能受体不同,这些接头前受体似乎不具有重要的生理学意义。大部分β-肾上腺素能受体介导的作用都涉及通过激动剂-受体复合物与Gs的相互作用而激活腺苷酸环化酶。

三种β-肾上腺素能受体蛋白均已被克隆,这些重组受体的特征与天然组织中已充分表征的三种β-肾上腺素能受体的特征相对应,称为β1、β2和β3。物种差异可能对β3-肾上腺素能受体具有重要影响,因为多种选择性β3-肾上腺素能受体激动剂可以激活啮齿动物的β3-肾上腺素能受体,但不能激活人的β3-肾上腺素能受体。β1-肾上腺素能受体具有多种亲和状态,这也许能够揭示β-肾上腺素能受体介导的心肌收缩的独特药理学特性。

许多实用的药理学工具可用于β-肾上腺素能受体表征,包括能够选择性激活β1-、β2-或β3-肾上腺素能受体的激动剂,以及三种亚型各自的选择性拮抗剂。尽管最初认为心脏刺激主要涉及β1-肾上腺素能受体,但现在认为可能涉及所有受体亚型。支气管扩张可能主要由β2-肾上腺素能受体介导。β3-肾上腺素能受体负责啮齿动物中白色脂肪组织的脂肪分解和棕色脂肪组织的产热作用。肾素释放可能是由于β1-肾上腺素能受体介导的。

β2-肾上腺素能受体激动剂通常被用作支气管扩张剂。选择性β3-肾上腺素能受体激动剂正在被开发用于治疗II型糖尿病、肥胖症和膀胱过度活动症。对β1-肾上腺素能受体不具有亚型选择性或具有选择性的β-肾上腺素能受体拮抗剂,被广泛用作抗高血压药,但其作用机制尚不明确。非选择性β-肾上腺素能受体拮抗剂眼内给药是常用的青光眼治疗方法。卡维地洛同时具有非选择性β受体阻断作用和α1受体阻断作用,最近被证明能够显著降低与充血性心力衰竭相关的死亡率/发病率。

缩写:

BRL 37344:(±)-(R*,R*)-(4-[2-([2-(3-氯苯基)-2-羟基乙基]氨基]丙基]苯氧基]乙酸盐
CGP20712A:(±)-2-羟基-5-[2-[[2-羟基-3-[4-[1-甲基-4-(三氟甲基)-1H-咪唑-2-基]苯氧基]丙基] -氨基]乙氧基] -苯甲酰胺甲磺酸盐
CL 316243:(R,R)-5-[2-[[2-(3-氯苯基)-2-羟乙基] -氨基] -丙基]1,3-苯并二氧杂戊-2,2-二甲酸二甲酯
ICI-118,551:(±)-1-[2,3-(二氢-7-甲基1H-茚-4-基)氧]-3-[(1-甲基乙基)氨基]-2-丁醇盐酸盐
ICYP:ICYP: 碘氰吲哚洛尔
SB-226552: (S)-4-{2-[2-羟基-3-(4-羟基苯氧基)丙胺基]乙基}苯氧基甲基环己基次膦酸
SR 58894:3-(2-烯丙基苯氧基)-1-[(1S)-1,2,3,4-四氢萘-1-基氨基]-(2S)-2-丙醇盐酸盐
SR 59230:3-(2-乙基苯氧基)-1-[(1S)-1,2,3,4-四-氢萘-1-基氨基)-(2S)-2-丙醇草酸盐
T-0509: [(–)-(R)-1-(3,4-二羟基苯基)-2-[(3,4-二甲氧基苯乙基)-氨基]乙醇

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1.
Girdlestone D. 2000. The IUPHAR compendium of receptor characterization and classification. 2. London: IUPHAR Media.
2.
Collins S. 2001. The -Adrenergic Receptors and the Control of Adipose Tissue Metabolism and Thermogenesis. Recent Progress in Hormone Research. 56(1):309-328. http://dx.doi.org/10.1210/rp.56.1.309
3.
Evans BA, Sato M, Sarwar M, Hutchinson DS, Summers RJ. 2010. Ligand-directed signalling at ?-adrenoceptors. 159(5):1022-1038. http://dx.doi.org/10.1111/j.1476-5381.2009.00602.x
4.
Zhang Y. 2012. Beta-adrenoceptor signaling pathways mediate cardiac pathological remodeling. Front Biosci. E4(5):1625-1637. http://dx.doi.org/10.2741/e484
5.
Gauthier C, Langin D, Balligand J. 2000. ?3-Adrenoceptors in the cardiovascular system. Trends in Pharmacological Sciences. 21(11):426-431. http://dx.doi.org/10.1016/s0165-6147(00)01562-5
6.
Hieble JP. 2000. Drugs targeting adrenergic receptors: does interaction with a specific subtype confer therapeutic advantage?. Curr Opin Drug Discov Devel. 3(4):370-82.
7.
Hieble JP, Bondinell W, Ruffolo RR. 1995. .alpha.- and .beta.-Adrenoceptors: From the Gene to the Clinic.Part 1.Molecular Biology and Adrenoceptor Subclassification. J. Med. Chem.. 38(18):3415-3444. http://dx.doi.org/10.1021/jm00018a001
8.
Joseph S, Colledge W, Kaumann A. 2004. Aspartate138 is required for the high-affinity ligand binding site but not for the low-affinity binding site of the ?1-adrenoceptor. Naunyn-Schmiedeberg's Arch Pharmacol. 370(3): http://dx.doi.org/10.1007/s00210-004-0962-1
9.
Kolinski M, Plazinska A, Jozwiak K. 2012. Recent Progress in Understanding of Structure, Ligand Interactions and the Mechanism of Activation of the β 2-Adrenergic Receptor. CMC. 19(8):1155-1163. http://dx.doi.org/10.2174/092986712799320547
10.
Ostrowski J, Kjelsberg MA, Caron MG, Lefkowitz RJ. 1992. Mutagenesis of the beta2-Adrenergic Receptor: How Structure Elucidates Function. Annu.Rev. Pharmacol.Toxicol.. 32(1):167-183. http://dx.doi.org/10.1146/annurev.pa.32.040192.001123
11.
Ruffolo RR, Bondinell W, Hieble JP. 1995. .alpha.- and .beta.-Adrenoceptors: From the Gene to the Clinic.2.Structure-Activity Relationships and Therapeutic Applications. J. Med. Chem.. 38(19):3681-3716. http://dx.doi.org/10.1021/jm00019a001
12.
Sato Y, Kurose H, Isogaya M, Nagao T. 1996. Molecular characterization of pharmacological properties of T-0509 for ?-adrenoceptors. European Journal of Pharmacology. 315(3):363-367. http://dx.doi.org/10.1016/s0014-2999(96)00648-6
13.
Sennitt MV, Kaumann AJ, Molenaar P, Beeley LJ, Young PW, Kelly J, Chapman H, Henson SM, Berge JM, Dean DK, et al. 1998. The contribution of classical (beta1/2-) and atypical beta-adrenoceptors to the stimulation of human white adipocyte lipolysis and right atrial appendage contraction by novel beta3-adrenoceptor agonists of differing selectivities. J Pharmacol Exp Ther. 285(3):1084-95.
14.
Takeda H, Yamazaki Y, Igawa Y, Kaidoh K, Akahane S, Miyata H, Nishizawa O, Akahane M, Andersson K. 2002. Effects of ?3-adrenoceptor stimulation on prostaglandin E2-induced bladder hyperactivity and on the cardiovascular system in conscious rats. Neurourol.Urodyn.. 21(6):558-565. http://dx.doi.org/10.1002/nau.10034
15.
Wehland M, Grosse J, Simonsen U, Infanger M, Bauer J, Grimm D. 2012. The Effects of Newer Beta-Adrenoceptor Antagonists on Vascular Function in Cardiovascular Disease. CVP. 10(3):378-390. http://dx.doi.org/10.2174/157016112799959323
16.
Weyer C, Tataranni PA, Snitker S, Danforth E, Ravussin E. 1998. Increase in insulin action and fat oxidation after treatment with CL 316,243, a highly selective beta3-adrenoceptor agonist in humans. Diabetes. 47(10):1555-1561. http://dx.doi.org/10.2337/diabetes.47.10.1555