孤啡肽/孤啡肽FQ和痛敏肽在调节脊髓神经传递中阿片受体样1受体的作用

The role of the ORL1 receptor in the modulation of spinal neurotransmission by nociceptin/orphanin FQ and nocistatin.

作者信息

Ahmadi S, Liebel J T, Zeilhofer H U

机构信息

Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, Fahrstrasse 17, D-91054, Erlangen, Germany.

出版信息

Eur J Pharmacol. 2001 Jan 19;412(1):39-44. doi: 10.1016/s0014-2999(00)00946-8.

DOI:10.1016/s0014-2999(00)00946-8

PMID:11166734

Abstract

Nociceptin/orphanin FQ and nocistatin are two neuropeptides with opposing effects on spinal neurotransmission and nociception. Nociceptin/orphanin FQ selectively suppresses excitatory glutamatergic neurotransmission, while nocistatin selectively interferes with glycinergic and gamma-aminobutyric acid (GABA)-ergic transmission. Here, we performed whole-cell patch-clamp recordings from superficial rat spinal cord dorsal horn neurons to investigate the role of the opioid receptor-like (ORL)1 receptor for modulatory actions of these peptides. The partial ORL1 receptor antagonist [phe1psi(CH(2)-NH)Gly(2)]nociceptin-(1-13)NH(2) competitively reversed the effects of nociceptin/orphanin FQ on excitatory neurotransmission (estimated pA(2) 6.43), but left the suppression of inhibitory synaptic transmission by nocistatin unaffected. These results indicate that the inhibitory action of nociceptin/orphanin FQ on glutamatergic transmission is mediated via ORL1 receptors, while nocistatin acts via a different so far unidentified receptor.

摘要

痛敏肽/孤啡肽FQ和痛抑素是两种对脊髓神经传递和痛觉具有相反作用的神经肽。痛敏肽/孤啡肽FQ选择性抑制兴奋性谷氨酸能神经传递，而痛抑素则选择性干扰甘氨酸能和γ-氨基丁酸（GABA）能传递。在此，我们对大鼠脊髓背角浅层神经元进行全细胞膜片钳记录，以研究阿片样受体（ORL）1受体在这些肽调节作用中的作用。部分ORL1受体拮抗剂[苯丙氨酸1ψ（CH₂-NH）甘氨酸2]痛敏肽-（1-13）NH₂竞争性逆转了痛敏肽/孤啡肽FQ对兴奋性神经传递的作用（估计pA₂为6.43），但对痛抑素对抑制性突触传递的抑制作用没有影响。这些结果表明，痛敏肽/孤啡肽FQ对谷氨酸能传递的抑制作用是通过ORL1受体介导的，而痛抑素则通过一种迄今尚未确定的不同受体发挥作用。