Regaya I, Pham T, Andreotti N, Sauze N, Carrega L, Martin-Eauclaire M F, Jouirou B, Peragut J C, Vacher H, Rochat H, Devaux C, Sabatier J M, Guieu R
UMR FRE CNRS 2738 Ingénierie des Protéines, Faculté de Médecine Nord, Bd P, Dramard 13015 Marseille, France.
Life Sci. 2004 Dec 10;76(4):367-77. doi: 10.1016/j.lfs.2004.06.023.
It has been shown that A2A adenosine receptors are implicated in pain modulation. The precise mechanism by which activation of A2A receptors produces analgesic effects, however, remains unclear. The aim of this study was to investigate the possible involvement of apamin-sensitive calcium-activated potassium channels (SKCa) and voltage-gated potassium (Kv) channels in A2A receptor activation-induced analgesic effects. Using mice, we evaluated the influence of apamin, a non specific blocker of SKCa channels, Lei-Dab7 (an analog of scorpion Leiurotoxin), a selective blocker of SKCa2 channels, and kaliotoxin (KTX) a Kv channel blocker, on the CGS 21680 (A2A adenosine receptor agonist)-induced increases in hot plate and tail pinch latencies. All drugs were injected in mice via the intracerebroventricular route. We found that apamin and Lei-Dab7, but not KTX, reduced antinociception produced by CGS21680 on the hot plate and tail pinch tests in a dose dependent manner. Lei-Dab 7 was more potent than apamin in this regard. We conclude that SKCa but not Kv channels are implicated in CGS 21680-induced antinociception.
已有研究表明,A2A腺苷受体与疼痛调节有关。然而,A2A受体激活产生镇痛作用的确切机制仍不清楚。本研究的目的是探讨蜂毒明肽敏感的钙激活钾通道(SKCa)和电压门控钾通道(Kv)在A2A受体激活诱导的镇痛作用中可能的参与情况。我们使用小鼠,评估了蜂毒明肽(SKCa通道的非特异性阻滞剂)、Lei-Dab7(蝎毒Leiurotoxin的类似物,SKCa2通道的选择性阻滞剂)和钾通道阻滞剂卡利毒素(KTX)对CGS 21680(A2A腺苷受体激动剂)诱导的热板和夹尾潜伏期延长的影响。所有药物均通过脑室内途径注射到小鼠体内。我们发现,蜂毒明肽和Lei-Dab7,但不是KTX,以剂量依赖性方式降低了CGS21680在热板和夹尾试验中产生的抗伤害感受作用。在这方面,Lei-Dab 7比蜂毒明肽更有效。我们得出结论,SKCa通道而非Kv通道参与了CGS 21680诱导的抗伤害感受作用。