Pauwels R A, Joos G F
Department of Respiratory Diseases, University Hospital Ghent, Belgium.
Arch Int Pharmacodyn Ther. 1995 Jan-Feb;329(1):151-60.
Adenosine causes bronchoconstriction both in vivo and in vitro in human asthmatics. In an in vivo rat model of adenosine-induced bronchoconstriction, the order of bronchoconstrictor potency of adenosine analogues was NECA = CPA > APNEA > CHA > R-PIA > CGS21680. This order of potency does not fit with the classical order of potency for a single subtype of adenosine receptors. The complete lack of bronchoconstrictory activity of CGS21680 suggests, nevertheless, that the A2A receptor subtype is not involved in the adenosine-induced bronchoconstriction. A remarkable finding was the dose-response curve to APNEA, which is thought to have some selective activity on the A3 receptor. The A2A-selective antagonist KF17837 (10(-7) to 10(-5) mol/kg) had no significant inhibitory activity on the adenosine-induced bronchoconstriction. The A1 antagonists, KF15372 and KW3902, both significantly inhibited the NECA-induced bronchoconstriction in BDE rats. We, therefore, conclude that the adenosine-induced bronchoconstriction in the rat is most likely due to binding of adenosine to different receptor subtypes including the A1, A2B and A3 subtypes.
腺苷在体内和体外均可引起人类哮喘患者支气管收缩。在腺苷诱导支气管收缩的大鼠体内模型中，腺苷类似物的支气管收缩效力顺序为NECA = CPA > APNEA > CHA > R - PIA > CGS21680。这种效力顺序与单一亚型腺苷受体的经典效力顺序不符。然而，CGS21680完全缺乏支气管收缩活性表明，A2A受体亚型不参与腺苷诱导的支气管收缩。一个显著的发现是APNEA的剂量 - 反应曲线，APNEA被认为对A3受体具有一些选择性活性。A2A选择性拮抗剂KF17837（10⁻⁷至10⁻⁵mol/kg）对腺苷诱导的支气管收缩没有显著的抑制活性。A1拮抗剂KF15372和KW3902均显著抑制了BDE大鼠中NECA诱导的支气管收缩。因此，我们得出结论，大鼠体内腺苷诱导的支气管收缩很可能是由于腺苷与包括A1、A2B和A3亚型在内的不同受体亚型结合所致。
