腺苷受体

腺苷受体(Adenosine receptor)，或称为P1受体(P1 receptors)^[1]，是一类以腺苷为内源性配体的嘌呤能G蛋白偶联受体。^[2]人体中腺苷受体有四种已知类型：A₁、A_2A、A_2B和A₃；每个都由不同的基因编码。

腺苷受体因其拮抗剂咖啡因和茶碱而闻名，它们对受体的作用产生了咖啡、茶和巧克力的刺激提神作用。

药理学

每种腺苷受体都具有不同的功能，但也有部分重叠， ^[3] 例如A₁和A_2A都在心脏中调节心肌耗氧量和冠状动脉血流量，但A_2A受体在全身具有更广泛的抗炎作用。 ^[4] 这两种受体在大脑中也起着重要作用， ^[5] 可调节其他神经递质例如多巴胺和谷氨酸的释放。而A_2B和A₃受体主要位于外周，参与炎症和免疫等。 ^[6]^[7]^[8]

大多数较老的作用于腺苷受体的化合物都是非选择性的，内源性激动剂腺苷同时在心脏中的四种腺苷受体作用而直接减缓心跳速度^[9] ，被用于治疗严重的心率过速；^[10] 腺苷还作用于大脑中的A₁和A_2A受体产生镇静作用。咖啡因和茶碱等黄嘌呤衍生物作为腺苷受体的非选择性拮抗剂具有与腺苷相反的作用，造成兴奋和心率加快。^[11] 这些化合物还充当磷酸二酯酶抑制剂，产生额外的抗炎作用，并使它们在医学上可用于治疗哮喘等疾病，但不太适合用于科学研究。^[12]

较新的腺苷受体激动剂和拮抗剂更加有效及具有亚型选择性，并且可以对阻断或刺激单个腺苷受体亚型的效果进行广泛的研究，目前新一代更具选择性的药物具有许多潜在的医疗用途。其中一些化合物仍然衍生自腺苷或黄嘌呤，但该领域的研究人员也发现了许多结构完全不同的选择性腺苷受体配体，为未来的研究提供了广泛的方向。^[13]^[14]

参考资料

^ Fredholm BB, Abbracchio MP, Burnstock G, Dubyak GR, Harden TK, Jacobson KA, Schwabe U, Williams M. Towards a revised nomenclature for P1 and P2 receptors. Trends Pharmacol. Sci. 1997, 18 (3): 79–82. PMC 4460977 . PMID 9133776. doi:10.1016/S0165-6147(96)01038-3.
^ Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol. Rev. 2001, 53 (4): 527–52 [2020-10-31]. PMID 11734617. （原始内容存档于2018-12-03）.
^ Gao ZG, Jacobson KA. Emerging adenosine receptor agonists. Expert Opinion on Emerging Drugs. September 2007, 12 (3): 479–92 [2023-08-23]. PMID 17874974. doi:10.1517/14728214.12.3.479. （原始内容存档于2021-11-25）.
^ Haskó G, Pacher P. A2A receptors in inflammation and injury: lessons learned from transgenic animals. Journal of Leukocyte Biology. March 2008, 83 (3): 447–55. PMC 2268631 . PMID 18160539. doi:10.1189/jlb.0607359.
^ Kalda A, Yu L, Oztas E, Chen JF. Novel neuroprotection by caffeine and adenosine A(2A) receptor antagonists in animal models of Parkinson's disease. Journal of the Neurological Sciences. October 2006, 248 (1–2): 9–15. PMID 16806272. doi:10.1016/j.jns.2006.05.003.
^ Fuxe K, Ferré S, Genedani S, Franco R, Agnati LF. Adenosine receptor-dopamine receptor interactions in the basal ganglia and their relevance for brain function. Physiology & Behavior. September 2007, 92 (1–2): 210–7. PMID 17572452. doi:10.1016/j.physbeh.2007.05.034.
^ Schiffmann SN, Fisone G, Moresco R, Cunha RA, Ferré S. Adenosine A2A receptors and basal ganglia physiology. Progress in Neurobiology. December 2007, 83 (5): 277–92. PMC 2148496 . PMID 17646043. doi:10.1016/j.pneurobio.2007.05.001.
^ Cunha RA, Ferré S, Vaugeois JM, Chen JF. Potential therapeutic interest of adenosine A2A receptors in psychiatric disorders. Current Pharmaceutical Design. 2008, 14 (15): 1512–24. PMC 2423946 . PMID 18537674. doi:10.2174/138161208784480090.
^ Cohen MV, Downey JM. Adenosine: trigger and mediator of cardioprotection. Basic Research in Cardiology. May 2008, 103 (3): 203–15. PMID 17999026. doi:10.1007/s00395-007-0687-7.
^ Peart JN, Headrick JP. Adenosinergic cardioprotection: multiple receptors, multiple pathways. Pharmacology & Therapeutics. May 2007, 114 (2): 208–21. PMID 17408751. doi:10.1016/j.pharmthera.2007.02.004.
^ Ferré S. An update on the mechanisms of the psychostimulant effects of caffeine. Journal of Neurochemistry. May 2008, 105 (4): 1067–79. PMID 18088379. doi:10.1111/j.1471-4159.2007.05196.x .
^ Osadchii OE. Myocardial phosphodiesterases and regulation of cardiac contractility in health and cardiac disease. Cardiovascular Drugs and Therapy. June 2007, 21 (3): 171–94. PMID 17373584. doi:10.1007/s10557-007-6014-6.
^ Baraldi PG, Tabrizi MA, Gessi S, Borea PA. Adenosine receptor antagonists: translating medicinal chemistry and pharmacology into clinical utility. Chemical Reviews. January 2008, 108 (1): 238–63. PMID 18181659. doi:10.1021/cr0682195.
^ Cristalli G, Lambertucci C, Marucci G, Volpini R, Dal Ben D. A2A adenosine receptor and its modulators: overview on a druggable GPCR and on structure-activity relationship analysis and binding requirements of agonists and antagonists. Current Pharmaceutical Design. 2008, 14 (15): 1525–52. PMID 18537675. doi:10.2174/138161208784480081.

外部链接

Adenosine Receptors. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. （原始内容存档于2016-10-24）.
医学主题词表（MeSH）：Adenosine+Receptors

[pmid9133776-1] Fredholm BB, Abbracchio MP, Burnstock G, Dubyak GR, Harden TK, Jacobson KA, Schwabe U, Williams M. Towards a revised nomenclature for P1 and P2 receptors. Trends Pharmacol. Sci. 1997, 18 (3): 79–82. PMC 4460977 . PMID 9133776. doi:10.1016/S0165-6147(96)01038-3.

[pmid11734617-2] Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol. Rev. 2001, 53 (4): 527–52 [2020-10-31]. PMID 11734617. （原始内容存档于2018-12-03）.

[pmid17874974-3] Gao ZG, Jacobson KA. Emerging adenosine receptor agonists. Expert Opinion on Emerging Drugs. September 2007, 12 (3): 479–92 [2023-08-23]. PMID 17874974. doi:10.1517/14728214.12.3.479. （原始内容存档于2021-11-25）.

[pmid18160539-4] Haskó G, Pacher P. A2A receptors in inflammation and injury: lessons learned from transgenic animals. Journal of Leukocyte Biology. March 2008, 83 (3): 447–55. PMC 2268631 . PMID 18160539. doi:10.1189/jlb.0607359.

[pmid16806272-5] Kalda A, Yu L, Oztas E, Chen JF. Novel neuroprotection by caffeine and adenosine A(2A) receptor antagonists in animal models of Parkinson's disease. Journal of the Neurological Sciences. October 2006, 248 (1–2): 9–15. PMID 16806272. doi:10.1016/j.jns.2006.05.003.

[pmid17572452-6] Fuxe K, Ferré S, Genedani S, Franco R, Agnati LF. Adenosine receptor-dopamine receptor interactions in the basal ganglia and their relevance for brain function. Physiology & Behavior. September 2007, 92 (1–2): 210–7. PMID 17572452. doi:10.1016/j.physbeh.2007.05.034.

[pmid17646043-7] Schiffmann SN, Fisone G, Moresco R, Cunha RA, Ferré S. Adenosine A2A receptors and basal ganglia physiology. Progress in Neurobiology. December 2007, 83 (5): 277–92. PMC 2148496 . PMID 17646043. doi:10.1016/j.pneurobio.2007.05.001.

[pmid18537674-8] Cunha RA, Ferré S, Vaugeois JM, Chen JF. Potential therapeutic interest of adenosine A2A receptors in psychiatric disorders. Current Pharmaceutical Design. 2008, 14 (15): 1512–24. PMC 2423946 . PMID 18537674. doi:10.2174/138161208784480090.

[pmid17999026-9] Cohen MV, Downey JM. Adenosine: trigger and mediator of cardioprotection. Basic Research in Cardiology. May 2008, 103 (3): 203–15. PMID 17999026. doi:10.1007/s00395-007-0687-7.

[pmid17408751-10] Peart JN, Headrick JP. Adenosinergic cardioprotection: multiple receptors, multiple pathways. Pharmacology & Therapeutics. May 2007, 114 (2): 208–21. PMID 17408751. doi:10.1016/j.pharmthera.2007.02.004.

[pmid18088379-11] Ferré S. An update on the mechanisms of the psychostimulant effects of caffeine. Journal of Neurochemistry. May 2008, 105 (4): 1067–79. PMID 18088379. doi:10.1111/j.1471-4159.2007.05196.x .

[pmid17373584-12] Osadchii OE. Myocardial phosphodiesterases and regulation of cardiac contractility in health and cardiac disease. Cardiovascular Drugs and Therapy. June 2007, 21 (3): 171–94. PMID 17373584. doi:10.1007/s10557-007-6014-6.

[pmid18181659-13] Baraldi PG, Tabrizi MA, Gessi S, Borea PA. Adenosine receptor antagonists: translating medicinal chemistry and pharmacology into clinical utility. Chemical Reviews. January 2008, 108 (1): 238–63. PMID 18181659. doi:10.1021/cr0682195.

[pmid18537675-14] Cristalli G, Lambertucci C, Marucci G, Volpini R, Dal Ben D. A2A adenosine receptor and its modulators: overview on a druggable GPCR and on structure-activity relationship analysis and binding requirements of agonists and antagonists. Current Pharmaceutical Design. 2008, 14 (15): 1525–52. PMID 18537675. doi:10.2174/138161208784480081.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]