Activation of neuronal adenosine A1 receptors suppresses secretory reflexes in the guinea pig colon
Activation of neuronal adenosine A1 receptors suppresses secretory reflexes in the guinea pig colon
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DOI：
10.1152/ajpgi.1999.276.2.g451
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发表时间：
1999-02-01
影响因子：
4.5
通讯作者：
Christofi, FL
中科院分区：
文献类型：
--
作者：
Cooke, HJ;Wang, YZ;Christofi, FL
在豚鼠结肠中研究了腺苷 A(1) 受体 (A(1)R) 在指示氯离子分泌的反射诱发短路电流 (I-sc) 中的作用。 A1R 拮抗剂 8-环戊茶碱 (CPT) 增强反射诱发的 I-sc。腺苷脱氨酶和核苷转运抑制剂 S-(4-硝基苯甲基)-6-硫代肌苷分别增强和减少反射诱导的 I-sc。 A(1)R 激动剂 2-氯-N-6-环戊基腺苷 (CCPA) 在纳摩尔浓度下抑制反射诱发的 I-sc，其作用被 CPT 拮抗。在存在阻断 6-羟色胺 (5-HT) 介导途径的 N-乙酰基-5-羟基色氨酸-5-羟基色氨酸酰胺或阻断前列腺素介导途径的吡罗昔康的情况下，CCPA 减少了残余反射诱发的 I-sc。 CCPA 降低了对 5-HT 脉冲的反应，但不影响河豚毒素不敏感的 I-sc 对卡巴胆碱或毛喉素的反应。在神经蛋白基因产物 9.5-免疫反应性（或 S-100 阴性）粘膜下神经元、神经胶质细胞和粘膜肌层的膜（10% 的神经元）和细胞质（90% 的神经元）中检测到 A(1)R 的免疫反应性。尽管用腺苷脱氨酶或 CPT 预孵育，大多数神经元细胞质中的 A(1)R 免疫反应性仍然升高。 A(1)R 免疫反应性共定位于突触素免疫反应性突触前静脉曲张神经末梢。结果表明，内源性腺苷与粘膜下神经元上的高亲和力 A(1)R 结合，起到生理制动器的作用，抑制反射诱发的指示氯离子分泌的 I-sc。
The role of adenosine A(1) receptors (A(1)R) in reflex-evoked short-circuit current (I-sc) indicative of chloride secretion was studied in the guinea pig colon. The A1R antagonist 8-eyclopentyltheophylline (CPT) enhanced reflex-evoked I-sc. Adenosine deaminase and the nucleoside transport inhibitor S-(4-nitrobenzyl)-6-thioinosine enhanced and reduced reflex-induced I-sc, respectively. The A(1)R agonist 2-chloro-N-6-cyclopentyladenosine (CCPA) inhibited reflex-evoked I-sc at nanomolar concentrations, and its action was antagonized by CPT. in the presence of either N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide to block the 6-hydroxytryptamine (5-HT)-mediated pathway or piroxicam to block the prostaglandin-mediated pathway, CCPA reduced the residual reflex-evoked I-sc. CCPA reduced the response to a 5-HT pulse without affecting the tetrodotoxin-insensitive I-sc responses to carbachol or forskolin. Immunoreactivity for A(1)R was detected in the membrane (10% of neurons) and cytoplasm (90% of neurons) of neural protein gene product 9.5-immunoreactive (or S-100-negative) submucosal neurons, in glia, and in the muscularis mucosa. A(1)R immunoreactivity in a majority of neurons remained elevated in the cytoplasm despite preincubation with adenosine deaminase or CPT. A(1)R immunoreactivity colocalized in synaptophysin-immunoreactive presynaptic varicose nerve terminals. The results indicate that endogenous adenosine binding to high-affinity A(1)R on submucosal neurons acts as a physiological brake to suppress reflex-evoked I-sc indicative of chloride secretion.