Liu Yen-Chin, Wang Ya-Jean, Wu Pei-Yu, Wu Sheng-Nan
Department of Anesthesiology, National Cheng Kung University Medical College, Tainan, Taiwan.
Naunyn Schmiedebergs Arch Pharmacol. 2009 Feb;379(2):127-35. doi: 10.1007/s00210-008-0353-0. Epub 2008 Sep 26.
The hyperpolarization-activated cation current (I (h)) in rat pituitary lactotrophs (GH(3) cells) was characterized. Tramadol-induced block of this current was investigated. Effects of various related compounds on I (h) in GH(3) cells were also compared. Tramadol caused a time- and concentration-dependent reduction in the amplitude of I (h) with an IC(50) value of 13.6 microM. ZD7288 (30 microM), CsCl (2 mM), and propofol (30 microM) were effective in suppressing the amplitude of I (h). 2',5'-dideoxyadenosine (100 microM) suppressed I (h), while sp-cAMPS (100 microM) had no effect on it. Tramadol (10 microM) shifted the activation curve of I (h) to a more negative potential by approximately -20 mV, although no change in the slope factor was observed. Under current-clamp configuration, tramadol (10 microM) could reduce the firing frequency of action potentials. Intracellular Ca(2+) measurements revealed its ability to reduce spontaneous Ca(2+) oscillations in GH(3) cells. The results suggests that during cell exposure to tramadol used at clinically relevant concentration, the tramadol-mediated inhibition of I (h) could be direct and mediated via a non-opioid mechanism and would be one of the ionic mechanisms underlying reduced cell excitability.
对大鼠垂体催乳素细胞（GH(3)细胞）中的超极化激活阳离子电流（I (h)）进行了表征。研究了曲马多对该电流的阻断作用。还比较了各种相关化合物对GH(3)细胞中I (h)的影响。曲马多导致I (h)幅度呈时间和浓度依赖性降低，IC(50)值为13.6 microM。ZD7288（30 microM）、CsCl（2 mM）和丙泊酚（30 microM）可有效抑制I (h)的幅度。2',5'-二脱氧腺苷（100 microM）可抑制I (h)，而sp-cAMPS（100 microM）对其无影响。曲马多（10 microM）使I (h)的激活曲线向更负的电位移动约-20 mV，尽管未观察到斜率因子的变化。在电流钳配置下，曲马多（10 microM）可降低动作电位的发放频率。细胞内Ca(2+)测量显示其能够减少GH(3)细胞中的自发Ca(2+)振荡。结果表明，在细胞暴露于临床相关浓度的曲马多时，曲马多介导的对I (h)的抑制可能是直接的且通过非阿片类机制介导，并且将是细胞兴奋性降低的离子机制之一。
