Chu X, Xu N, Li P, Wang J Q
Department of Physiology, Shanghai Medical University, China.
Eur J Pharmacol. 1999 Jan 1;364(1):49-53. doi: 10.1016/s0014-2999(98)00816-4.
The recently available antagonist selective for novel nociceptin receptor, [Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2, was utilized in this study to verify specificity of nociceptin receptor in mediating the nociceptin-induced inhibition of electrical activity of neurons in the rostral ventrolateral medulla of rat brain slices. Perfusion of nociceptin (10 nM) considerably reduced spontaneously firing frequency of the medullary neurons. Co-perfusion of [Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2 (10 microM) completely blocked the nociceptin-induced depression of the neuronal activity. Blocking effect of [Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2 was concentration-dependent. However, the nociceptin antagonist did not modify basal, and opioid peptide enkephalin-depressed, firing rates of the neurons. In contrast to [Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2, the non-selective opioid receptor antagonist naloxone (10 microM) failed to affect the nociceptin inhibition even though naloxone at a lower concentration (1 microM) readily blocked enkephalin-induced depression of the neuronal activity. These data indicate that the nociceptin-induced inhibition of spontaneous discharge of the rostral ventrolateral medulla neurons is specifically mediated by [Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2-sensitive nociceptin receptors distinct from typical naloxone-sensitive opioid receptors.
本研究使用了最近可得的对新型孤啡肽受体具有选择性的拮抗剂[Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2，以验证孤啡肽受体在介导孤啡肽诱导的大鼠脑片延髓头端腹外侧区神经元电活动抑制中的特异性。灌注孤啡肽（10 nM）可显著降低延髓神经元的自发放电频率。共同灌注[Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2（10 microM）可完全阻断孤啡肽诱导的神经元活动抑制。[Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2的阻断作用呈浓度依赖性。然而，孤啡肽拮抗剂并未改变神经元的基础放电率以及阿片肽脑啡肽抑制的放电率。与[Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2不同，非选择性阿片受体拮抗剂纳洛酮（10 microM）未能影响孤啡肽的抑制作用，尽管较低浓度（1 microM）的纳洛酮可轻易阻断脑啡肽诱导的神经元活动抑制。这些数据表明，孤啡肽诱导的延髓头端腹外侧区神经元自发放电抑制是由[Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2敏感的孤啡肽受体特异性介导的，不同于典型的纳洛酮敏感的阿片受体。
