Abdulla F A, Smith P A
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Neuroscience. 1999 Mar;89(1):43-60. doi: 10.1016/s0306-4522(98)00443-6.
Damage to sensory nerves invokes the expression of neuropeptide Y in the cell bodies of sensory neurons in dorsal root ganglia. We therefore compared the action of this peptide on control dorsal root ganglia neurons with its action on neurons from animals in which the sciatic nerve had been cut. Neuropeptide Y (0.1-1.0 microM) increased the excitability of 24% of control neurons and its effect was stronger and more cells (56%) were affected after axotomy. Increased excitability was mediated via a Y2-receptor and resulted from attenuation of Ca2+-sensitive K+-conductance(s) secondary to suppression of N-type Ca2+ channel current. Y1-agonists potentiated L-type Ca2+ channel current in control neurons without altering excitability. This Y1-effect was attenuated whereas effects mediated via Y2-receptors were enhanced after axotomy. No evidence was found for involvement of Y4- or Y5-receptor subtypes in the actions of neuropeptide Y either on control or on axotomized dorsal root ganglion neurons. It is concluded that neuropeptide Y increases the excitability of sensory neurons by interacting with a Y2-receptor and thereby decreasing N-type Ca2+ channel current and Ca2+-sensitive K+-conductance(s). When peripheral nerves are damaged, dorsal root ganglion neurons start to express neuropeptide Y and its excitatory Y2-excitatory effects are enhanced. The peptide may therefore contribute to the generation of aberrant sensory activity and perhaps to the etiology of injury-induced neuropathic pain.
感觉神经损伤会引发背根神经节中感觉神经元细胞体中神经肽Y的表达。因此，我们比较了这种肽对对照背根神经节神经元的作用与其对坐骨神经已被切断的动物的神经元的作用。神经肽Y（0.1 - 1.0微摩尔）增加了24%的对照神经元的兴奋性，并且在轴突切断后其作用更强，更多细胞（56%）受到影响。兴奋性增加是通过Y2受体介导的，并且是由于N型钙通道电流受抑制后钙敏感钾电导减弱所致。Y1激动剂增强对照神经元中的L型钙通道电流，但不改变兴奋性。这种Y1效应在轴突切断后减弱，而通过Y2受体介导的效应增强。未发现Y4或Y5受体亚型参与神经肽Y对对照或轴突切断的背根神经节神经元的作用。结论是神经肽Y通过与Y2受体相互作用增加感觉神经元的兴奋性，从而降低N型钙通道电流和钙敏感钾电导。当周围神经受损时，背根神经节神经元开始表达神经肽Y，其兴奋性Y2效应增强。因此，该肽可能有助于异常感觉活动的产生，也许还与损伤诱导的神经性疼痛的病因有关。
