Chiu T H, Chen T Y, Ho C L, Chiang S T
Department of Physiology, National Yang-Ming Medical College, Taipei, R.O.C.
Neuropharmacology. 1990 Aug;29(8):747-55. doi: 10.1016/0028-3908(90)90128-e.
Intracellular recording was used to study the effects of dermorphin on neurons of the locus coeruleus in the rat, in a totally submerged brain slice preparation. Dermorphin caused the inhibition of spontaneous firing of all neurons of the locus coeruleus tested, with an IC50 of 7 nM. Based on the inhibition of spontaneous firing rate, dermorphin was 16.5 times more potent than morphine. Larger concentrations of dermorphin (30-100 nM) further hyperpolarized the neurons of the locus coeruleus and simultaneously caused a reduction in input resistance. These effects were antagonized by naloxone, with a dissociation equilibrium constant of 0.8 nM. The hyperpolarization of neurons of the locus coeruleus, caused by dermorphin, was reversed at a membrane potential of -112 mV in this preparation. Furthermore, this hyperpolarization was blocked by cesium chloride and barium chloride. Thus, these data suggest that dermorphin binds to mu-opioid receptors on the cell membrane of neurons of the locus coeruleus. This leads to opening of the inward-going rectification potassium channels, resulting in the observed hyperpolarization of the membrane.
在全浸没脑片制备中，采用细胞内记录法研究了皮啡肽对大鼠蓝斑核神经元的影响。皮啡肽可抑制所有受试蓝斑核神经元的自发放电，半数抑制浓度（IC50）为7 nM。基于对自发放电频率的抑制作用，皮啡肽的效力是吗啡的16.5倍。更高浓度的皮啡肽（30 - 100 nM）可使蓝斑核神经元进一步超极化，同时导致输入电阻降低。这些效应可被纳洛酮拮抗，解离平衡常数为0.8 nM。在此制备中，皮啡肽引起的蓝斑核神经元超极化在膜电位为 -112 mV时被逆转。此外，这种超极化可被氯化铯和氯化钡阻断。因此，这些数据表明皮啡肽与蓝斑核神经元细胞膜上的μ-阿片受体结合。这导致内向整流钾通道开放，从而产生所观察到的膜超极化。
