Fleetwood-Walker S M, Parker R M, Munro F E, Young M R, Hope P J, Mitchell R
Department of Preclinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies, University of Edinburgh, UK.
Eur J Pharmacol. 1993 Sep 28;242(2):173-81. doi: 10.1016/0014-2999(93)90077-u.
Since the NK2 receptor-selective tachykinin, neurokinin A is present in fine primary afferent neurons in addition to the NK1 receptor-selective tachykinin, substance P, we have addressed the relative role of NK1 and NK2 receptors in somatosensory processing in spinal dorsal horn. Recording extracellularly from rat laminae III-V neurons whilst ionophoresing drugs nearby, the selective NK1 receptor antagonists L 688,169, GR 82334 and [D-Pro4,D-Trp7,910Phe11]substance P-(4-11) failed to influence neuronal responses to cutaneous pinch or noxious heat but often enhanced responses to innocuous brush. In contrast, the highly selective NK2 receptor antagonist L 659,874 profoundly inhibited responses to noxious heat but not pinch or brush. Highly selective synthetic agonists for both NK1 and NK2 receptors ([N-acetyl-Arg6,Sar9,Met(O2)11]substance P-(6-11) and GR 64349, respectively) and also NKA showed the inverse effects on sensory responses to those brought about by their antagonists. At higher ionophoretic currents, both NK1 and NK2 receptor agonists increased spontaneous activity. This increased basal firing induced by GR 64349 and neurokinin A (but not that due to [N-acetyl-Arg6,Sar9,Met(O2)11]substance P-(6-11) appeared to partially pre-empt further excitatory responses to noxious heat. It is concluded that although both NK1 and NK2 receptors can clearly mediate excitation of dorsal horn neurons, it is not NK1, but rather NK2 receptors that are important as the physiological transducer of brief thermal nociceptive inputs in this model.
由于NK2受体选择性速激肽神经激肽A与NK1受体选择性速激肽P物质一样，都存在于细小的初级传入神经元中，因此我们研究了NK1和NK2受体在脊髓背角躯体感觉处理中的相对作用。在对附近进行离子电渗给药的同时，对大鼠III - V层神经元进行细胞外记录，选择性NK1受体拮抗剂L 688,169、GR 82334和[D - Pro4，D - Trp7,9,10，Phe11]P物质 - (4 - 11)未能影响神经元对皮肤夹捏或有害热刺激的反应，但常常增强对无害轻刷刺激的反应。相反，高度选择性的NK2受体拮抗剂L 659,874则显著抑制对有害热刺激的反应，但对夹捏或轻刷刺激无影响。NK1和NK2受体的高度选择性合成激动剂（分别为[N - 乙酰 - Arg6，Sar9，Met(O2)11]P物质 - (6 - 11)和GR 64349）以及神经激肽A对感觉反应的影响与其拮抗剂所产生的影响相反。在较高的离子电渗电流下，NK1和NK2受体激动剂均增加自发活动。GR 64349和神经激肽A诱导的这种基础放电增加（但不是[N - 乙酰 - Arg6，Sar9，Met(O2)11]P物质 - (6 - 11)引起的）似乎部分抢先占据了对有害热刺激的进一步兴奋反应。由此得出结论，虽然NK1和NK2受体都能明显介导背角神经元的兴奋，但在该模型中，作为短暂热伤害性传入生理转导器的重要受体不是NK1，而是NK2受体。
