Yang Y R, Lee E H, Chiu T H
Department of Physiology, National Yang-Ming University, Shih-Pai, Taipei, Taiwan.
Eur J Pharmacol. 1998 Jun 12;351(1):23-30. doi: 10.1016/s0014-2999(98)00296-9.
The effect of Tyr-D-Arg-Phe-Sar (TAPS), a mu-selective tetrapeptide analog of dermorphin, was studied in the rat both in vitro, using slices of the locus coeruleus, and in vivo, after microinjection into the locus coeruleus. In electrophysiological studies, TAPS (1-100 nM) was able to inhibit spontaneous firing, cause hyperpolarization of the membrane potential and reduce the input resistance of neurons of the locus coeruleus, suggesting that there was an effect on the potassium channels. Based on the inhibition of the spontaneous firing rate, the average IC50 for TAPS was calculated to be 1.9 nM, a value lower than that reported for dermorphin or morphine. The TAPS-induced effects were antagonized by naloxone, with a dissociation equilibrium constant of 1.96 +/- 0.14 nM. The results indicate that TAPS binds to mu-opioid receptors on the cell membrane of neurons of the locus coeruleus to cause its inhibitory actions. In behavioral study, TAPS was microinjected bilaterally via chronically implanted cannulae into the locus coeruleus of non-anesthetized rats and its effects on locomotor activity determined. TAPS, at concentrations of 1 microM and 10 microM, but not of 0.1 microM, induced hypolocomotion/sedation and the effect was significantly reversed by naloxone (5 mg/kg i.p.). Taken together, these data suggest that TAPS has an inhibitory effect on neurons of the locus coeruleus and produces hypolocomotive/sedative effects in vivo.
研究了Tyr-D-Arg-Phe-Sar（TAPS），一种皮啡肽的μ选择性四肽类似物，在大鼠体内外的作用。体外实验使用蓝斑核切片，体内实验则是将其微量注射到蓝斑核中。在电生理研究中，TAPS（1-100 nM）能够抑制自发放电，引起膜电位超极化并降低蓝斑核神经元的输入电阻，表明其对钾通道有作用。根据对自发放电频率的抑制作用，计算出TAPS的平均半数抑制浓度（IC50）为1.9 nM，该值低于皮啡肽或吗啡的报道值。TAPS诱导的效应被纳洛酮拮抗，解离平衡常数为1.96±0.14 nM。结果表明，TAPS与蓝斑核神经元细胞膜上的μ阿片受体结合以产生其抑制作用。在行为学研究中，通过长期植入的套管将TAPS双侧微量注射到未麻醉大鼠的蓝斑核中，并测定其对运动活动的影响。浓度为1μM和10μM而非0.1μM的TAPS诱导运动减少/镇静，且该效应被纳洛酮（5 mg/kg腹腔注射）显著逆转。综上所述，这些数据表明TAPS对蓝斑核神经元有抑制作用，并在体内产生运动减少/镇静作用。
