Nakamura I, Ohta Y, Kemmotsu O
Department of Anesthesiology and Intensive Care, Hokkaido University School of Medicine, Sapporo, Japan.
Anesthesiology. 1997 Sep;87(3):577-84. doi: 10.1097/00000542-199709000-00018.
Adenosine analogs have been shown to produce antinociception after intrathecal administration. To determine the adenosine receptor subtype involved in spinal antinociception, the effects of selective agonists and an antagonist on the evoked potentials recorded from a neonatal rat spinal cord were studied. The measured potentials are a slow ventral root potential (slow VRP), which is the C-fiber-evoked excitatory response associated with nociceptive information; a monosynaptic reflex (MSR), which reflects a non-nociceptive transmission related to motor function; and a dorsal root potential (DRP), which reflects a gamma-aminobutyric acidA (GABA(A)) receptor-mediated presynaptic inhibition associated with analgesia.
The evoked potentials were recorded in response to electric stimulation of a lumbar dorsal root. Dose-response curves of agonists for these responses were obtained to determine their relative potency order. The antagonist dissociation constants (K(D) values) were estimated by Schild analysis.
Adenosine agonists dose dependently inhibited the slow VRP and the MSR. However, the slow VRP was five to eight times more sensitive to them than was the MSR. The rank order of agonist potency was N6-cyclohexyladenosine (CHA) = N6-(R)-phenylisopropyladenosine (R-PIA) > 5'-N-ethylcarboxamidoadenosine (NECA) >> CGS 21680 in both responses. 8-Cyclopentyltheophylline produced dose-dependent parallel shifts to the right of NECA dose-response curves for these responses. Schild analysis gave linear plots with slopes near unity. The K(D) values of CPT for the MSR and the slow VRP were estimated to be 5.5 nM and 4.3 nM, respectively. The DRP was also depressed by adenosine agonists with potency order of CHA > NECA >> CGS 21680. 8-Cyclopentyltheophylline antagonized the inhibitory effects of CHA on the DRP.
The results indicate that adenosine agonists inhibit spinal sensory transmission related to nociception by acting at the A1 receptors. The A1 receptor also seems to be involved in transmission related to the spinal motor system. Feedback inhibition mediated by GABA(A) receptors does not contribute to this antinociceptive action.
鞘内注射腺苷类似物已被证明可产生抗伤害感受作用。为确定参与脊髓抗伤害感受的腺苷受体亚型，研究了选择性激动剂和拮抗剂对新生大鼠脊髓记录的诱发电位的影响。所测量的电位包括慢腹根电位（慢VRP），它是与伤害性信息相关的C纤维诱发的兴奋性反应；单突触反射（MSR），它反映与运动功能相关的非伤害性传递；以及背根电位（DRP），它反映与镇痛相关的γ-氨基丁酸A（GABAA）受体介导的突触前抑制。
记录对腰段背根电刺激的诱发电位。获得这些反应的激动剂剂量-反应曲线以确定它们的相对效价顺序。通过Schild分析估计拮抗剂解离常数（KD值）。
腺苷激动剂剂量依赖性地抑制慢VRP和MSR。然而，慢VRP对它们的敏感性比MSR高五到八倍。在两种反应中，激动剂效价顺序为N6-环己基腺苷（CHA）= N6-（R）-苯基异丙基腺苷（R-PIA）> 5'-N-乙基羧酰胺腺苷（NECA）>> CGS 21680。8-环戊基茶碱使这些反应的NECA剂量-反应曲线剂量依赖性地平行右移。Schild分析给出斜率接近1的线性图。MSR和慢VRP的CPT的KD值估计分别为5.5 nM和4.3 nM。DRP也被腺苷激动剂抑制，效价顺序为CHA > NECA >> CGS 21680。8-环戊基茶碱拮抗CHA对DRP的抑制作用。
结果表明腺苷激动剂通过作用于A1受体抑制与伤害感受相关的脊髓感觉传递。A1受体似乎也参与与脊髓运动系统相关的传递。GABAA受体介导的反馈抑制对这种抗伤害感受作用没有贡献。
