腺苷受體

腺苷受體(Adenosine receptor)，或稱為P1受體(P1 receptors)^[1]，是一類以腺苷為內源性配體的嘌呤能G蛋白偶聯受體。^[2]人體中腺苷受體有四種已知類型：A₁、A_2A、A_2B和A₃；每個都由不同的基因編碼。

腺苷受體因其拮抗劑咖啡因和茶鹼而聞名，它們對受體的作用產生了咖啡、茶和巧克力的刺激提神作用。

藥理學

每種腺苷受體都具有不同的功能，但也有部分重疊， ^[3] 例如A₁和A_2A都在心臟中調節心肌耗氧量和冠狀動脈血流量，但A_2A受體在全身具有更廣泛的抗炎作用。 ^[4] 這兩種受體在大腦中也起着重要作用， ^[5] 可調節其他神經遞質例如多巴胺和穀氨酸的釋放。而A_2B和A₃受體主要位於外周，參與炎症和免疫等。 ^[6]^[7]^[8]

大多數較老的作用於腺苷受體的化合物都是非選擇性的，內源性激動劑腺苷同時在心臟中的四種腺苷受體作用而直接減緩心跳速度^[9] ，被用於治療嚴重的心率過速；^[10] 腺苷還作用於大腦中的A₁和A_2A受體產生鎮靜作用。咖啡因和茶鹼等黃嘌呤衍生物作為腺苷受體的非選擇性拮抗劑具有與腺苷相反的作用，造成興奮和心率加快。^[11] 這些化合物還充當磷酸二酯酶抑制劑，產生額外的抗炎作用，並使它們在醫學上可用於治療哮喘等疾病，但不太適合用於科學研究。^[12]

較新的腺苷受體激動劑和拮抗劑更加有效及具有亞型選擇性，並且可以對阻斷或刺激單個腺苷受體亞型的效果進行廣泛的研究，目前新一代更具選擇性的藥物具有許多潛在的醫療用途。其中一些化合物仍然衍生自腺苷或黃嘌呤，但該領域的研究人員也發現了許多結構完全不同的選擇性腺苷受體配體，為未來的研究提供了廣泛的方向。^[13]^[14]

參考資料

^ 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. （原始內容存檔於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. （原始內容存檔於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.

外部連結

Adenosine Receptors. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. （原始內容存檔於2016-10-24）.
醫學主題詞表（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. （原始內容存檔於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. （原始內容存檔於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.

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