Structure-activity relationship for the endogenous cannabinoid, anandamide, and certain of its analogues at vanilloid receptors in transfected cells and vas deferens
Structure-activity relationship for the endogenous cannabinoid, anandamide, and certain of its analogues at vanilloid receptors in transfected cells and vas deferens
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DOI：
10.1038/sj.bjp.0703850
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发表时间：
2001-02-01
影响因子：
7.3
通讯作者：
Pertwee, RG
中科院分区：
文献类型：
--
作者：
Ross, RA;Gibson, TM;Pertwee, RG
1本研究旨在探索大麻素及其某些类似物与转染细胞中大鼠VR 1受体的结构-活性关系，并研究大麻素与小鼠输精管中CB 1和香草素受体相互作用的相对程度。2 pK（i）rVR 1转染CHO细胞膜上[H-3]-树脂毒素的置换值对于大麻素来说显着较小（5.78）比其结构类似物N-（4-羟基苯基）-花生四烯酰胺（AM404; 6.18）和N-（3 -甲氧基-4-羟基）苄基-花生四烯酰胺（arvanil; 6.77）。3对于刺激Ca-45（2+）摄取到rVR 1转染的CHO细胞中的pEC（50）值，花生四烯酸酰胺（5.80）显著低于AM404（6.32）或arvanil（9.29）。Arvanil也比辣椒素（pEC（50）= 7.37）更有效，辣椒素是一种具有与Arvanil相同的取代苄基极性头基的化合物。4在小鼠输精管中，树脂毒素作为电诱发收缩的抑制剂比辣椒素有效218倍。辣椒平对两种药物的拮抗程度相似（pK（B）分别为6.93和7.18），但SR 141716 A（1 μ M）不拮抗。与辣椒碱相比，大麻素对辣椒平的拮抗作用不敏感（pK（B）= 6.02），对SR 141716 A的拮抗作用不敏感（pK（B）=8.66），对甲大麻素的拮抗作用不敏感（pK（B）=9.56）。WIN 55212被SR 141716 A拮抗（pK（B）=9.02），但不被辣椒平（10 μ M）拮抗。5总之，大麻素及其某些类似物对大鼠VR 1受体具有亲和力和效力。在小鼠输精管，这似乎表达香草酸和CB 1受体，这两种受体类型似乎有助于anandamide诱导的抑制诱发收缩。
1 This study was directed at exploring the structure-activity relationship for anandamide and certain of its analogues at the rat VR1 receptor in transfected cells and at investigating the relative extent to which anandamide interacts with CB1 and vanilloid receptors in the mouse vas deferens.2 pK(i) values for displacement of [H-3]-resiniferatoxin from membranes of rVR1 transfected CHO cells were significantly less for anandamide (5.78) than for its structural analogues N-(4 hydroxyphenyl)-arachidonylamide (AM404; 6.18) and N-(3 -methoxy-4-hydroxy)benzyl-arachidonylamide (arvanil; 6.77).3 pEC(50) values for stimulating Ca-45(2+) uptake into rVR1 transfected CHO cells were significantly less for anandamide (5.80) than for AM404 (6.32) or arvanil (9.29). Arvanil was also significantly more potent than capsaicin (pEC(50) = 7.37), a compound with the same substituted benzyl polar head group as arvanil.4 In the mouse vas deferens, resiniferatoxin was 218 times more potent than capsaicin as an inhibitor of electrically-evoked contractions. Both drugs were antagonized to a similar extent by capsazepine (pK(B)=6.93 and 7.18 respectively) but were not antagonized by SR141716A (1 muM). Anandamide was less susceptible than capsaicin to antagonism by capsazepine (pK(B) = 6.02) and less susceptible to antagonism by SR141716A (pK(B)=8.66) than methanandamide (pK(B)=9.56). WIN55212 was antagonized by SR141716A (pK(B)=9.02) but not by capsazepine (10 muM).5 In conclusion, anandamide and certain of its analogues have affinity and efficacy at the rat VR1 receptor. In the mouse vas deferens, which seems to express vanilloid and CB1 receptors, both receptor types appear to contribute to anandamide-induced inhibition of evoked contractions.