Lundy P M, Frew R
Can J Physiol Pharmacol. 1981 Jun;59(6):520-7. doi: 10.1139/y81-078.
Effects of ketamine on responses to sympathomimetic amines were studied using isolated aortic and pulmonary artery strips from the rabbit. Ketamine (1.1 x 10(-5) to 3.7 x 10(-4) M) potentiated adrenaline-contracted strips. Potentiation was not impaired in tissues from animals pretreated with reserpine, with 6-hydroxydopamine, or its tissues pretreated with cocaine. Pretreatment of the strips with the catechol O-methyltransferase (COMT) inhibitors tropolone or pyrogallol or the inhibitor of extraneuronal uptake 17 beta-estradiol blocked the potentiation by ketamine; in addition, potentiation by the COMT and extraneuronal uptake inhibitors was abolished or greatly reduced by ketamine. In rabbit aorta, ketamine potentiated responses to the catecholamines (adrenaline greater than nordefrine greater than noradrenaline) but not to the noncatecholamines phenylephrine, methoxamine, and synephrine; instead a slight relaxant effect was observed. Ketamine potentiated, whereas cocaine inhibited, responses to tyramine Experiments using the technique of oil immersion demonstrated that ketamine reduced the rate at which aortic strips inactivate adrenaline even when monoamine oxidase (MAO) and neuronal uptake processes were fully inhibited. Uptake studies showed that ketamine and 17 beta-estradiol reduced extraneuronal accumulation of [3H]adrenaline in aortic strips. We conclude that ketamine is an inhibitor of extraneuronal uptake in the vascular smooth muscles studied and the importance of this mechanism in producing its known cardiovascular effect is discussed.
使用兔离体主动脉和肺动脉条研究了氯胺酮对拟交感胺反应的影响。氯胺酮（1.1×10⁻⁵至3.7×10⁻⁴M）增强了肾上腺素收缩的条带。在用利血平、6-羟基多巴胺预处理的动物组织或用可卡因预处理的组织中，增强作用未受损害。用儿茶酚-O-甲基转移酶（COMT）抑制剂托酚酮或连苯三酚或神经外摄取抑制剂17β-雌二醇预处理条带可阻断氯胺酮的增强作用；此外，COMT和神经外摄取抑制剂的增强作用被氯胺酮消除或大大降低。在兔主动脉中，氯胺酮增强了对儿茶酚胺（肾上腺素＞去甲麻黄碱＞去甲肾上腺素）的反应，但对非儿茶酚胺苯肾上腺素、甲氧明和辛弗林无增强作用；相反，观察到轻微的舒张作用。氯胺酮增强而可卡因抑制对酪胺的反应。使用油浸技术的实验表明，即使单胺氧化酶（MAO）和神经元摄取过程被完全抑制，氯胺酮仍可降低主动脉条使肾上腺素失活的速率。摄取研究表明，氯胺酮和17β-雌二醇减少了主动脉条中[³H]肾上腺素的神经外积累。我们得出结论，氯胺酮是所研究的血管平滑肌中神经外摄取的抑制剂，并讨论了该机制在产生其已知心血管效应中的重要性。
