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首页> 外文期刊>The European Journal of Neuroscience >TRPV1 and CB receptor-mediated effects of the endovanilloid/endocannabinoid N-arachidonoyl-dopamine on primary afferent fibre and spinal cord neuronal responses in the rat.
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TRPV1 and CB receptor-mediated effects of the endovanilloid/endocannabinoid N-arachidonoyl-dopamine on primary afferent fibre and spinal cord neuronal responses in the rat.

机译：TRPV1和CB受体介导的内皮素/内源性大麻素N-花生四烯酰基-多巴胺对大鼠初级传入纤维和脊髓神经元反应的影响。

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Abstract N-arachidonoyl-dopamine (NADA) is an endogenous ligand at TRPV1 and CB(1) receptors, which are expressed on primary afferent nociceptors. The aim of this study was to determine contributions of proposed pronociceptive TRPV1 and antinociceptive CB(1) receptors to effects of peripheral NADA on primary afferent fibre function. Effects of NADA on primary afferent nociceptor function, determined by whole cell patch clamp and calcium imaging studies of adult dorsal root ganglion (DRG) neurons, were determined. Application of NADA (1 micro m) to DRG neurons depolarized the resting membrane potential (Vm) from -58 +/- 1 to -44 +/- 3 mV (P < 0.00001) and evoked a significant increase (P < 0.0001) in intracellular calcium (74 +/- 11% of response to 60 mm KCl), compared to basal. The TRPV1 receptor antagonist capsazepine abolished NADA-evoked depolarization of Vm (P < 0.0001) and NADA-evoked calcium responses (P < 0.001), which were also blocked by the CB(1) receptor antagonist SR141716A (P < 0.001). Effects of NADA (1.5 micro g and 5 micro g/50 micro L) on mechanically evoked responses of dorsal horn neurons in anaesthetized Sprague-Dawley rats were studied. Intraplantar injection of the higher dose of NADA (5 micro g/50 micro L) studied significantly inhibited innocuous (8, 10 g) mechanically evoked responses of dorsal horn neurons compared to vehicle, effects blocked by intraplantar injection of SR141716A. Higher weight (26-100 g) noxious-evoked responses of dorsal horn neurons were also significantly inhibited by NADA (5 micro g/50 micro L), effects blocked by intraplantar injection of the TRPV1 antagonist, iodo-resiniferatoxin. NADA has a complex pattern of effects on DRG neurons and primary afferent fibres, which is likely to reflect its dual site of action at TRPV1 and CB(1) receptors and the differential expression of these receptors by primary afferent fibres.
机译：摘要N-花生四烯酸-多巴胺（NADA）是TRPV1和CB（1）受体上的内源性配体，它们在初级传入伤害感受器上表达。这项研究的目的是确定拟议的伤害感受性TRPV1和抗伤害感受性CB（1）受体对外周NADA对初级传入纤维功能的影响。确定了NADA对成年背根神经节（DRG）神经元的全细胞膜片钳和钙成像研究确定的初级传入伤害感受器功能的影响。将NADA（1微米）应用于DRG神经元可使静息膜电位（Vm）从-58 +/- 1减至-44 +/- 3 mV（P <0.00001），并引起显着增加（P <0.0001）。与基础相比，细胞内钙（对60 mm KCl的反应为74 +/- 11％）。 TRPV1受体拮抗剂辣椒素废除了NADA引起的Vm去极化（P <0.0001）和NADA引起的钙反应（P <0.001），也被CB（1）受体拮抗剂SR141716A（P <0.001）阻断。研究了NADA（1.5 micro g和5 micro g / 50 micro L）对麻醉的Sprague-Dawley大鼠背角神经元机械诱发反应的影响。与媒介物相比，足底内注射较高剂量的NADA（5 micro g / 50 micro L）可显着抑制背角神经元的无害（8，10 g）机械诱发反应，而plant内注射SR141716A则可阻止这种作用。 NADA（5 micro g / 50 micro L）也明显抑制了体重较高的（26-100 g）背角神经元的有害诱发反应，这种作用被plant内注射TRPV1拮抗剂碘-树脂毒素结合了。 NADA对DRG神经元和初级传入纤维具有复杂的作用模式，这很可能反映了它在TRPV1和CB（1）受体上的双重作用位点以及初级传入纤维对这些受体的差异表达。

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