Spinal neuronal cannabinoid receptors mediate urodynamic effects of systemic fatty acid amide hydrolase (FAAH) inhibition in rats
Spinal neuronal cannabinoid receptors mediate urodynamic effects of systemic fatty acid amide hydrolase (FAAH) inhibition in rats
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DOI：
10.1002/nau.22753
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发表时间：
2016-04-01
影响因子：
2
通讯作者：
Hedlund, Petter
中科院分区：
文献类型：
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作者：
Fuellhase, Claudius;Schreiber, Andrea;Hedlund, Petter
目的检测全身性脂肪酸酰胺水解酶(FAAH)抑制对大鼠尿动力学的影响是否涉及脊髓大麻素1型(CB1)或2型(CB2)受体。观察静脉注射油酰乙胺(OEtA；FAAH抑制剂)0.3 mg/kg和鞘内注射(IT)5g利莫那班(CB1拮抗剂)或5g SR144528(CB2拮抗剂)对清醒大鼠尿动力学的影响。结果给予利莫那班或SR144528后，膀胱功能正常的无梗阻大鼠出现膀胱过度活动(BO)，OEtA可抑制BO。OEtA还能对抗梗阻大鼠的BO。SR144528对梗阻大鼠的膀胱功能无明显影响，但可拮抗OEtA的尿动力学效应。令人惊讶的是，利莫那班(和另一种CB1拮抗剂AM251)减少了梗阻大鼠的BO，此后OEtA没有产生额外的尿动力学效应。结论全身性抑制FAAH的尿动力学效应涉及脊髓神经元CB1和CB2受体的激活。内源性脊髓CB受体配体似乎调节正常排尿和BO。脊髓CB受体功能改变可能参与梗阻性BO的发病机制。诺鲁罗。乌罗代南。2016年，35：464-470。(C)2015年威利期刊公司。
AimsTo test if urodynamic effects from systemic Fatty Acid Amide Hydrolase (FAAH) inhibition involve sacral spinal cannabinoid type 1 (CB1) or type 2 (CB2) receptors.MethodsMale rats with or without partial urethral obstruction were used for cystometry or immunohistochemistry. Urodynamic effects of intravenous (IV) 0.3mg/kg Oleoyl Ethyl Amide (OEtA; FAAH inhibitor), and intrathecal (IT) 5g rimonabant (CB1 antagonist) or 5g SR144528 (CB2 antagonist) were studied in awake rats.ResultsAfter administration of rimonabant or SR144528, non-obstructed rats with normal bladder function developed bladder overactivity (BO), which was counteracted by OEtA. OEtA also counteracted BO in obstructed rats. SR144528 did not affect bladder function in obstructed rats but counteracted the urodynamic effects of OEtA. Surprisingly, rimonabant (and AM251, another CB1 antagonist) reduced BO in obstructed rats, whereafter OEtA produced no additional urodynamic effects. CB1 expression increased in the sacral spinal cord of obstructed rats whereas no changes were observed for CB2 or FAAH.ConclusionsUrodynamic effects of systemic FAAH inhibition involve activities at spinal neuronal CB1 and CB2 receptors in normal and obstructed rats. Endogenous spinal CB receptor ligands seem to regulate normal micturition and BO. Altered spinal CB receptor functions may be involved in the pathogenesis of obstruction-induced BO. Neurourol. Urodynam. 35:464-470, 2016. (c) 2015 Wiley Periodicals, Inc.