Production and physiological actions of anandamide in the vasculature of the rat kidney
Production and physiological actions of anandamide in the vasculature of the rat kidney
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DOI：
10.1172/jci119677
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发表时间：
1997-09-15
影响因子：
15.9
通讯作者：
Moore, LC
中科院分区：
文献类型：
--
作者：
Deutsch, DG;Goligorsky, MS;Moore, LC
内源性大麻素受体激动剂anandamide存在于中枢和外周组织中。由于肾脏含有降解大麻素的酰胺酶和大麻素受体的转录物，因此我们表征了大麻素信号系统的分子组分以及外源性大麻素在肾脏中的血管效应。我们发现，花生四烯酸是存在于肾匀浆，培养的肾内皮细胞（EC）和系膜细胞，这些细胞也含有花生四烯酸酰胺酶。逆转录酶PCR显示，EC含有大麻素1型（CB 1）受体的转录本，而系膜细胞有CB 1和CB 2受体的mRNA。EC表现出特异性，高亲和性的结合anandamide（Kd = 27.4 nM）。Anandamide（1 μ M）在体外灌流的延髓传入小动脉血管舒张;血管舒张可被L-NAME（0.1 mM）抑制一氧化氮（NO）合酶或SR 141716 A（1 μ M）拮抗CB 1受体阻断，但不能被吲哚美辛（10 μ M）阻断。Anandamide（10 nM）刺激CB 1受体介导的NO从灌注肾动脉段释放;在EC中观察到类似的效果。最后，花生四烯酸酰胺（1 μ M）产生一氧化氮介导的抑制KCl刺激的[H-3]去甲肾上腺素释放交感神经离体肾动脉段。因此，大麻素信号系统存在于肾脏中，在那里它发挥显著的血管舒张和神经调节作用。
The endogenous cannabinoid receptor agonist anandamide is present in central and peripheral tissues. As the kidney contains both the amidase that degrades anandamide and transcripts for anandamide receptors, we characterized the molecular components of the anandamide signaling system and the vascular effects of exogenous anandamide in the kidney. We show that anandamide is present in kidney homogenates, cultured renal endothelial cells (EC), and mesangial cells; these cells also contain anandamide amidase. Reverse-transcriptase PCR shows that EC contain transcripts for cannabinoid type 1 (CB1) receptors, while mesangial cells have mRNA for both CB1 and CB2 receptors. EC exhibit specific, high-affinity binding of anandamide (K-d = 27.4 nM). Anandamide (1 mu M) vasodilates juxtamedullary afferent arterioles perfused in vitro; the vasodilation can be blocked by nitric oxide (NO) synthase inhibition with L-NAME (0.1 mM) or CB1 receptor antagonism with SR 141716A (1 mu M), but not by indomethacin (10 mu M). Anandamide (10 nM) stimulates CB1-receptor-mediated NO release from perfused renal arterial segments; a similar effect was seen in EC. Finally, anandamide (1 mu M) produces a NO-mediated inhibition of KCl-stimulated [H-3]norepinephrine release from sympathetic nerves on isolated renal arterial segments. Hence, an anandamide signaling system is present in the kidney, where it exerts significant vasorelaxant and neuromodulatory effects.