Church M K, Featherstone R L, Cushley M J, Mann J S, Holgate S T
J Allergy Clin Immunol. 1986 Oct;78(4 Pt 2):670-5. doi: 10.1016/0091-6749(86)90044-8.
Methylxanthines have been used for the treatment of asthma for more than 60 years, but their mechanism of action is poorly understood. Their ability to inhibit cyclic adenosine monophosphate phosphodiesterase has attracted much attention. However, this is clearly demonstrable only in high doses and is more likely to be related to toxicity. An alternative mechanism is antagonism of adenosine receptors in the lung. Adenosine has been shown to be released in asthma and cause bronchoconstriction in patients with asthma. Its effects are selectively inhibited by concentrations of theophylline that do not block histamine-induced bronchoconstriction. Neither phosphodiesterase inhibition nor adenosine receptor antagonism explains the action of enprofylline in asthma. Consequently, additional actions of methylxanthines are likely to contribute to their beneficial effects. They may include adrenaline release from the adrenal medulla, an effect on cell calcium distribution, inhibition of the generation of contractile prostaglandins, and an improvement of diaphragmatic contractility.
甲基黄嘌呤用于治疗哮喘已有60多年，但人们对其作用机制了解甚少。它们抑制环磷酸腺苷磷酸二酯酶的能力备受关注。然而，这仅在高剂量时才能明确显示，且更可能与毒性有关。另一种机制是拮抗肺中的腺苷受体。已证明腺苷在哮喘发作时释放，并导致哮喘患者支气管收缩。其作用可被不阻断组胺诱导的支气管收缩的茶碱浓度选择性抑制。磷酸二酯酶抑制和腺苷受体拮抗都无法解释恩丙茶碱在哮喘中的作用。因此，甲基黄嘌呤的其他作用可能有助于其有益效果。这些作用可能包括肾上腺髓质释放肾上腺素、对细胞钙分布的影响、抑制收缩性前列腺素的生成以及改善膈肌收缩力。
