Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Br J Pharmacol. 2010 Mar;159(6):1247-63. doi: 10.1111/j.1476-5381.2009.00597.x. Epub 2010 Feb 2.
It is well known that adenine-based purines exert multiple effects on pain transmission. However, less attention has been given to the potential effects of guanine-based purines on pain transmission. The aim of this study was to investigate the effects of intraperitoneal (i.p.) and oral (p.o.) administration of guanosine on mice pain models. Additionally, investigation into the mechanisms of action of guanosine, its potential toxicity and cerebrospinal fluid (CSF) purine levels were also assessed.
Mice received an i.p. or p.o. administration of vehicle (0.1 mM NaOH) or guanosine (up to 240 mg x kg(-1)) and were evaluated in several pain models.
Guanosine produced dose-dependent antinociceptive effects in the hot-plate, glutamate, capsaicin, formalin and acetic acid models, but it was ineffective in the tail-flick test. Additionally, guanosine produced a significant inhibition of biting behaviour induced by i.t. injection of glutamate, AMPA, kainate and trans-ACPD, but not against NMDA, substance P or capsaicin. The antinociceptive effects of guanosine were prevented by selective and non-selective adenosine receptor antagonists. Systemic administration of guanosine (120 mg x kg(-1)) induced an approximately sevenfold increase on CSF guanosine levels. Guanosine prevented the increase on spinal cord glutamate uptake induced by intraplantar capsaicin.
This study provides new evidence on the mechanism of action of the antinociceptive effects after systemic administration of guanosine. These effects seem to be related to the modulation of adenosine A(1) and A(2A) receptors and non-NMDA glutamate receptors.
腺嘌呤类嘌呤对疼痛传递有多种影响，这是众所周知的。然而，人们对鸟嘌呤类嘌呤对疼痛传递的潜在影响关注较少。本研究旨在研究腹腔内（i.p.）和口服（p.o.）给予鸟苷对小鼠疼痛模型的影响。此外，还评估了鸟苷的作用机制、潜在毒性和脑脊液（CSF）嘌呤水平。
小鼠接受 i.p. 或 p.o. 给予载体（0.1 mM NaOH）或鸟苷（高达 240 mg x kg(-1))，并在几种疼痛模型中进行评估。
鸟苷在热板、谷氨酸、辣椒素、福尔马林和乙酸模型中产生剂量依赖性的镇痛作用，但在尾闪烁试验中无效。此外，鸟苷对 i.t. 注射谷氨酸、AMPA、 kainate 和 trans-ACPD 引起的咬行为有显著抑制作用，但对 NMDA、P 物质或辣椒素无效。鸟苷的镇痛作用被选择性和非选择性腺苷受体拮抗剂所阻止。系统给予鸟苷（120 mg x kg(-1))可使 CSF 鸟苷水平增加约七倍。鸟苷可防止足底注射辣椒素引起的脊髓谷氨酸摄取增加。
本研究为系统给予鸟苷后的镇痛作用的作用机制提供了新的证据。这些作用似乎与腺苷 A(1) 和 A(2A) 受体和非 NMDA 谷氨酸受体的调制有关。
