Department of Internal Medicine (Cardiology), College of Medicine, Chosun University, Gwangju 501-759, Korea.
Korean J Physiol Pharmacol. 2008 Jun;12(3):101-9. doi: 10.4196/kjpp.2008.12.3.101. Epub 2008 Jun 30.
The aim of the present study was to examine the effects of ketamine, a dissociative anesthetics, on secretion of catecholamines (CA) secretion evoked by cholinergic stimulation from the perfused model of the isolated rat adrenal gland, and to establish its mechanism of action, and to compare ketamine effect with that of thiopental sodium, which is one of intravenous barbiturate anesthetics. Ketamine (30~300microM), perfused into an adrenal vein for 60 min, dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high K(+) (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic NN receptor agonist, 100microM) and McN-A-343 (a selective muscarinic M1 receptor agonist, 100microM). Also, in the presence of ketamine (100microM), the CA secretory responses evoked by veratridine (a voltage-dependent Na(+) channel activator, 100microM), Bay-K-8644 (an L-type dihydropyridine Ca(2+) channel activator, 10microM), and cyclopiazonic acid (a cytoplasmic Ca(2+)-ATPase inhibitor, 10microM) were significantly reduced, respectively. Interestingly, thiopental sodium (100microM) also caused the inhibitory effects on the CA secretory responses evoked by ACh, high K(+) , DMPP, McN-A-343, veratridine, Bay-K-8644, and cyclopiazonic acid. Collectively, these experimental results demonstrate that ketamine inhibits the CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors and the membrane depolarization from the isolated perfused rat adrenal gland. It seems likely that the inhibitory effect of ketamine is mediated by blocking the influx of both Ca(2+) and Na(+) through voltage-dependent Ca(2+) and Na(+) channels into the rat adrenal medullary chromaffin cells as well as by inhibiting Ca(2+) release from the cytoplasmic calcium store, which are relevant to the blockade of cholinergic receptors. It is also thought that, on the basis of concentrations, ketamine causes similar inhibitory effect with thiopental in the CA secretion from the perfused rat adrenal medulla.
本研究旨在考察分离大鼠肾上腺灌流模型中，氯胺酮（一种分离麻醉剂）对乙酰胆碱刺激引起的儿茶酚胺（CA）分泌的影响，并确定其作用机制，并比较氯胺酮与硫喷妥钠（一种静脉内巴比妥类麻醉剂）的作用。氯胺酮（30~300μM）灌流肾上腺静脉 60 分钟，剂量和时间依赖性地抑制 ACh（5.32mM）、高 K+（直接膜去极化剂，56mM）、DMPP（选择性神经元烟碱 NN 受体激动剂，100μM）和 McN-A-343（选择性毒蕈碱 M1 受体激动剂，100μM）引起的 CA 分泌反应。此外，在氯胺酮（100μM）存在的情况下，veratridine（电压依赖性 Na+通道激活剂，100μM）、Bay-K-8644（L 型二氢吡啶 Ca2+通道激活剂，10μM）和环匹阿尼酸（细胞质 Ca2+-ATP 酶抑制剂，10μM）引起的 CA 分泌反应也明显减少。有趣的是，硫喷妥钠（100μM）也引起了对 ACh、高 K+、DMPP、McN-A-343、veratridine、Bay-K-8644 和环匹阿尼酸引起的 CA 分泌反应的抑制作用。总的来说，这些实验结果表明，氯胺酮抑制了刺激大鼠肾上腺灌流引起的 CA 分泌，包括乙酰胆碱（烟碱和毒蕈碱）受体和膜去极化。似乎氯胺酮的抑制作用是通过阻断电压依赖性 Ca2+和 Na+通道进入大鼠肾上腺髓质嗜铬细胞的 Ca2+和 Na+内流以及抑制细胞质钙库中 Ca2+的释放来介导的，这与胆碱能受体的阻断有关。也认为，基于浓度，氯胺酮在大鼠肾上腺髓质灌流中的 CA 分泌中引起与硫喷妥钠相似的抑制作用。
