Fedan J S, Belt J J, Yuan L X, Frazer D G
Physiology Section, National Institute for Occupational Safety and Health, Morgantown, West Virginia.
J Pharmacol Exp Ther. 1993 Jan;264(1):217-20.
In higher concentrations (> 3 x 10(-4) M) than those causing contractile responses. ATP relaxed the smooth muscle of the guinea pig perfused trachea. Here we examined the relaxant effects of nucleotides. ATP and its nonhydrolyzable congener, beta, gamma-methylene ATP (APPCP), were approximately 4- and approximately 117-fold, respectively, more potent when applied separately to the serosal (extraluminal, EL) surface compared to the mucosal (intraluminal, IL) surface of methacholine (3 x 10(-7) M; EL)-contracted tracheae. APPCP was orders of magnitude more potent than ATP in both EL and IL compartments. EL UTP did not cause relaxation; IL UTP was nearly devoid of activity. The order of EL and IL activity (APPCP >> ATP) was unusual for nucleotide-induced relaxation of smooth muscle. Relaxation to ATP was not inhibited by the Cl- channel blocker 4,4'-diisothiocyano-2,2'-stilbene disulfonate (10(-4) M) or by the cyclo-oxygenase inhibitor indomethacin (3 x 10(-6) M), in contrast to the inhibitory effects of these drugs on contraction to ATP. The adenosine receptor antagonist 8-phenyltheophylline (10(-6) M) had no effect on relaxation to ATP or APPCP. Our findings indicate that Cl- channels, prostaglandins and adenosine are not involved in relaxation to adenine nucleotides.
在高于引起收缩反应的浓度（>3×10⁻⁴ M）时，ATP可使豚鼠灌注气管的平滑肌舒张。在此，我们研究了核苷酸的舒张作用。与应用于乙酰甲胆碱（3×10⁻⁷ M；浆膜面）收缩的气管黏膜（管腔内，IL）表面相比，当分别应用于浆膜（管腔外，EL）表面时，ATP及其不可水解的类似物β,γ-亚甲基ATP（APPCP）的效力分别约高4倍和约117倍。在EL和IL区室中，APPCP的效力比ATP高几个数量级。EL表面的UTP不会引起舒张；IL表面的UTP几乎没有活性。对于核苷酸诱导的平滑肌舒张，EL和IL活性的顺序（APPCP >> ATP）是不寻常的。与这些药物对ATP收缩的抑制作用相反，ATP诱导的舒张不受Cl⁻通道阻滞剂4,4'-二异硫氰基-2,2'-二苯乙烯二磺酸（10⁻⁴ M）或环氧化酶抑制剂吲哚美辛（3×10⁻⁶ M）的抑制。腺苷受体拮抗剂8-苯基茶碱（10⁻⁶ M）对ATP或APPCP诱导的舒张没有影响。我们的研究结果表明，Cl⁻通道、前列腺素和腺苷不参与腺嘌呤核苷酸诱导的舒张。
