Dent G, Giembycz M A
Krankenhaus Grosshansdorf, Zentrum für Pneumologie und Thoraxchirurgie, Germany.
Thorax. 1996 Jun;51(6):647-9. doi: 10.1136/thx.51.6.647.
The second messenger cyclic nucleotides, cyclic AMP and cyclic GMP, mediate relaxation of airways smooth muscle and suppression of multiple inflammatory cell functions. The intracellular concentrations of these cyclic nucleotides are regulated by a superfamily of phosphodiesterase (PDE) enzymes which break down cAMP and cGMP and, thereby, affect airway tone and inflammation. Theophylline and other drugs that act through inhibition of PDE are currently the subject of great research interest, since the uncovering of their anti-inflammatory actions suggests a possible additional mode of action in inflammatory diseases such as asthma. The characterisation of multiple families of PDE isoenzymes with distinct tissue distributions has encouraged hope that selective PDE inhibitors can be developed which act at specific targets without exhibiting the side effects of non-selective inhibitors like theophylline. The combination of bronchodilator and anti-inflammatory properties in a single drug by selective inhibition of specific PDE isoenzymes could produce agents most efficacious in every way for asthma therapy.
第二信使环核苷酸，即环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP），介导气道平滑肌舒张并抑制多种炎症细胞功能。这些环核苷酸的细胞内浓度受磷酸二酯酶（PDE）超家族调控，该酶超家族可分解cAMP和cGMP，从而影响气道张力和炎症反应。茶碱及其他通过抑制PDE发挥作用的药物目前是大量研究的热点，因为其抗炎作用的发现提示了在哮喘等炎症性疾病中可能存在的另一种作用方式。多种具有不同组织分布的PDE同工酶家族的特征表明，有望开发出选择性PDE抑制剂，其作用于特定靶点而不表现出如茶碱等非选择性抑制剂的副作用。通过选择性抑制特定PDE同工酶，在单一药物中结合支气管扩张和抗炎特性，可能会产生在哮喘治疗各方面都最有效的药物。
