Spinal cord adenosine receptor stimulation in rats inhibits peripheral neutrophil accumulation - The role of N-methyl-D-aspartate receptors
Spinal cord adenosine receptor stimulation in rats inhibits peripheral neutrophil accumulation - The role of N-methyl-D-aspartate receptors
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DOI：
10.1172/jci119104
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发表时间：
1996-12-15
影响因子：
15.9
通讯作者：
Firestein, GS
中科院分区：
文献类型：
--
作者：
Bong, GW;Rosengren, S;Firestein, GS
在两种大鼠炎症模型中研究脊髓腺苷受体结扎对外周白细胞积聚的影响。通过鞘内导管注射腺苷A1受体激动剂可显著减少真皮炎症部位的神经浸润。这些作用可被N-甲基-D-天冬氨酸（NMDA）逆转，并可被谷氨酸受体拮抗剂（+/-）-2-氨基-5-磷酸戊酸（AP-5）模拟。在气囊渗出物中测量的外周腺苷水平在发炎的气囊中显著降低，但在用AP-5鞘内治疗后保持接近正常。此外，鞘内A（1）受体激动剂和AP-5的抗炎作用可被腹腔内注射的腺苷A（2）受体拮抗剂逆转。因此，中枢NMDA受体活性可通过降低腺苷（一种通过A（2）受体激活抑制中性粒细胞功能的类腺苷酸）的局部水平来调节外周炎症部位的中性粒细胞蓄积。这代表了一种以前未知的中枢神经系统影响炎症反应的途径。
The effect of spinal adenosine receptor ligation on peripheral leukocyte accumulation was studied in two rat models of inflammation. Neutrophil infiltration into dermal inflammatory sites was signficantly reduced by adenosine A(1) receptor agonists injected through intrathecal catheters. These effects were reversed by N-methyl-D-aspartate (NMDA), and were mimicked by (+/-)-2-amino-5-phosphonopentanoic acid (AP-5), a glutamate NR;IDA receptor antagonist. Peripheral adenosine levels, as measured in air pouch exudates, decreased markedly in inflamed pouches but remained near normal after intrathecal treatment with AP-5. Moreover, the antiinflammatory effects of intrathecal A(1) receptor agonists and AP-5 were reversed by an adenosine A(2) receptor antagonist administered intraperitoneally. Hence, central NMDA receptor activity can regulate neutrophil accumulation in peripheral inflammatory sites by reducing local levels of adenosine, an antiinflammatory autacoid which inhibits neutrophil function through A(2) receptor activation. This represents a previously unknown pathway by which the central nervous system influences inflammatory responses.