前列腺素E2通过EP3受体调节咳嗽：对未来咳嗽治疗的意义
2009/12/15
基础理论：部分严重哮喘患者和慢性阻塞性肺疾病患者对β2肾上腺受体激动剂和糖皮质激素的反应较差，而且长期使用上述药物也存在一些安全性方面的问题。哮喘患者吸入前列腺素E2治疗同时具有抗炎和支气管扩张作用，但也能导致咳嗽。
目的：本研究通过一系列体内和体外试验方法，研究了参与前列腺素E2诱导的感觉神经活化及咳嗽的相关受体。
检测指标和主要结果：通过应用一系列药理学工具，我们发现EP3受体介导了前列腺素E2诱导的人、小鼠和豚鼠感觉神经去极化过程。此外，数据显示，来源于EP3缺陷小鼠[Ptger3 (-/-)]的迷走神经对前列腺素E2无反应。同时，体内实验显示，EP3受体拮抗剂能抑制前列腺素E2诱发的咳嗽。
结论：研究介导前列腺素E2相关咳嗽受体是开发具有抗炎和支气管作用但无其它副作用药物的关键步骤。
（刘国梁 审校）
Am J Respir Crit Care Med. 2009 Sep 3.
Prostaglandin E2 Mediates cough via the EP3 Receptor: Implications for Future Disease Therapy.
Maher SA, Birrell MA, Belvisi MG.
RATIONALE: A significant population of severe asthmatic and chronic obstructive pulmonary disease patients are less responsive to beta2-adrenoceptor agonists and corticosteroids and there are possible safety issues concerning long term use of these drugs. Inhaled prostaglandin E2 is both anti-inflammatory and a bronchodilator in asthmatic patients but also causes cough.
OBJECTIVES: We aim to identify the receptor involved in prostaglandin E2-induced sensory nerve activation and cough using a range of in vitro and in vivo techniques. Methods,
MEASUREMENTS AND MAIN RESULTS: Using an extensive range of pharmacological tools we have identified that the EP3 receptor mediates prostaglandin E2-induced depolarization of sensory nerves in human, mouse and guinea-pig. Further supporting evidence comes from data showing responses to prostaglandin E2 are virtually abolished in isolated vagus nerves from EP3-deficient mice (Ptger3 (-/-)). Finally we demonstrate the role of the EP3 receptor in vivo using a selective EP3 antagonist to attenuate prostaglandin E2-induced cough.
CONCLUSION: Identification of the receptor mediating prostaglandin E2-induced cough represents a key step in developing a drug that is anti-inflammatory and a bronchodilator but without unwanted side effects.
Maher SA, Birrell MA, Belvisi MG. Am J Respir Crit Care Med. 2009 Sep 3.
目的：本研究通过一系列体内和体外试验方法，研究了参与前列腺素E2诱导的感觉神经活化及咳嗽的相关受体。
检测指标和主要结果：通过应用一系列药理学工具，我们发现EP3受体介导了前列腺素E2诱导的人、小鼠和豚鼠感觉神经去极化过程。此外，数据显示，来源于EP3缺陷小鼠[Ptger3 (-/-)]的迷走神经对前列腺素E2无反应。同时，体内实验显示，EP3受体拮抗剂能抑制前列腺素E2诱发的咳嗽。
结论：研究介导前列腺素E2相关咳嗽受体是开发具有抗炎和支气管作用但无其它副作用药物的关键步骤。
（刘国梁 审校）
Am J Respir Crit Care Med. 2009 Sep 3.
Prostaglandin E2 Mediates cough via the EP3 Receptor: Implications for Future Disease Therapy.
Maher SA, Birrell MA, Belvisi MG.
RATIONALE: A significant population of severe asthmatic and chronic obstructive pulmonary disease patients are less responsive to beta2-adrenoceptor agonists and corticosteroids and there are possible safety issues concerning long term use of these drugs. Inhaled prostaglandin E2 is both anti-inflammatory and a bronchodilator in asthmatic patients but also causes cough.
OBJECTIVES: We aim to identify the receptor involved in prostaglandin E2-induced sensory nerve activation and cough using a range of in vitro and in vivo techniques. Methods,
MEASUREMENTS AND MAIN RESULTS: Using an extensive range of pharmacological tools we have identified that the EP3 receptor mediates prostaglandin E2-induced depolarization of sensory nerves in human, mouse and guinea-pig. Further supporting evidence comes from data showing responses to prostaglandin E2 are virtually abolished in isolated vagus nerves from EP3-deficient mice (Ptger3 (-/-)). Finally we demonstrate the role of the EP3 receptor in vivo using a selective EP3 antagonist to attenuate prostaglandin E2-induced cough.
CONCLUSION: Identification of the receptor mediating prostaglandin E2-induced cough represents a key step in developing a drug that is anti-inflammatory and a bronchodilator but without unwanted side effects.
Maher SA, Birrell MA, Belvisi MG. Am J Respir Crit Care Med. 2009 Sep 3.
