Faber E S, Chambers J P, Evans R H, Henderson G
Department of Pharmacology, School of Medical Sciences, Bristol.
Br J Pharmacol. 1996 Sep;119(2):189-90. doi: 10.1111/j.1476-5381.1996.tb15969.x.
The present study explored the action of nociceptin, the putative endogenous ligand for the orphan opioid receptor (ORL1), on the rat hemisected spinal cord preparation. Electrical stimulation of a dorsal root evokes a glutamatergic population ventral root potential (DR-VRP) in the corresponding ventral root. Low intensity stimulation evokes two A fibre-mediated components; a compound action potential of motoneurones superimposed on a population e.p.s.p. (excitatory postsynaptic potential); at higher stimulus intensities sufficient to activate C fibres a more prolonged population e.p.s.p. is evoked. All three components were depressed by nociceptin in a concentration-dependent manner with IC50 values (s.e.mean) of 119 +/- 2 nM (n = 4), 241 +/- 3 nM (n = 4) and 32 +/- 2 nM (n = 4), respectively. The depressant actions of nociceptin (30 nM and 300 nM) were not reversed by the opioid antagonist naloxone (1 microM). Nociceptin (100 nM and 300 nM) had no effect on the afferent volleys in the dorsal root. Nociceptin therefore appears to be acting as an inhibitory peptide at the spinal level through a naloxone-insensitive opioid receptor.
本研究探讨了孤啡肽（一种假定的孤儿阿片受体（ORL1）内源性配体）对大鼠脊髓半横切标本的作用。电刺激背根可在相应腹根诱发谷氨酸能群体腹根电位（DR-VRP）。低强度刺激可诱发两个由A纤维介导的成分；运动神经元的复合动作电位叠加在群体兴奋性突触后电位（e.p.s.p.）上；在足以激活C纤维的较高刺激强度下，可诱发更持久的群体e.p.s.p.。所有这三个成分均被孤啡肽以浓度依赖性方式抑制，IC50值（标准误均值）分别为119±2 nM（n = 4）、241±3 nM（n = 4）和32±2 nM（n = 4）。阿片受体拮抗剂纳洛酮（1 μM）不能逆转孤啡肽（30 nM和300 nM）的抑制作用。孤啡肽（100 nM和300 nM）对背根传入冲动无影响。因此，孤啡肽似乎通过一种对纳洛酮不敏感的阿片受体在脊髓水平发挥抑制性肽的作用。
