Mueller R A, Widerlöv E, Breese G R
Pharmacol Biochem Behav. 1984 Aug;21(2):289-96. doi: 10.1016/0091-3057(84)90228-4.
Intracerebroventricular (ICV) administration of the stable adenosine analogue 2-chloroadenosine (2CA) to hyperoxic halothane-anesthetized rats produced a dose-dependent depression of respiration largely as a result of a decrease in tidal volume. Similar changes were noted after another adenosine analogue, phenylisopropyladenosine (PIA). Higher doses shifted the minute ventilation-PaCO2 curve to the right and decreased its slope. Bradycardia and hypotension were produced at doses which altered respiration. Neonatal destruction of brain serotonin or dopamine-containing nerve terminals did not alter the 2CA-induced respiratory depression. Naloxone significantly antagonized the respiratory and circulatory changes produced by 2CA though the changes produced by PIA were not significantly antagonized. Peripherally and intracerebroventricularly administered theophylline were largely ineffective in reversing the 2CA-induced respiratory depression. Thus, these data suggest that a major part of the respiratory depression produced by 2CA is due to indirect activation of opioid receptors. In contrast, very little of the respiratory depression after PIA is via mechanisms antagonized by naloxone. Thus, putative adenosine agonists appear to vary in the extent to which respiratory depression is provoked by interactions with opioid systems.
向高氧氟烷麻醉的大鼠脑室内（ICV）注射稳定的腺苷类似物2-氯腺苷（2CA），会产生剂量依赖性的呼吸抑制，这主要是由于潮气量减少所致。另一种腺苷类似物苯异丙基腺苷（PIA）注射后也观察到类似变化。较高剂量会使分钟通气量-PaCO2曲线右移并降低其斜率。在改变呼吸的剂量下会出现心动过缓和低血压。新生大鼠脑内5-羟色胺或含多巴胺神经末梢的破坏并不会改变2CA诱导的呼吸抑制。纳洛酮可显著拮抗2CA引起的呼吸和循环变化，不过PIA引起的变化未被纳洛酮显著拮抗。外周和脑室内注射氨茶碱在很大程度上无法逆转2CA诱导的呼吸抑制。因此，这些数据表明，2CA引起的呼吸抑制主要部分是由于阿片受体的间接激活。相比之下，PIA引起的呼吸抑制很少是通过纳洛酮拮抗的机制。因此，假定的腺苷激动剂在与阿片系统相互作用引发呼吸抑制的程度上似乎有所不同。
