内源性脂质花生四烯酸乙醇胺是人类香草酸受体（hVR1）的完全激动剂。
The endogenous lipid anandamide is a full agonist at the human vanilloid receptor (hVR1).
作者信息
Smart D, Gunthorpe M J, Jerman J C, Nasir S, Gray J, Muir A I, Chambers J K, Randall A D, Davis J B
机构信息
Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, U.K.
出版信息
Br J Pharmacol. 2000 Jan;129(2):227-30. doi: 10.1038/sj.bjp.0703050.
The endogenous cannabinoid anandamide was identified as an agonist for the recombinant human VR1 (hVR1) by screening a large array of bioactive substances using a FLIPR-based calcium assay. Further electrophysiological studies showed that anandamide (10 or 100 microM) and capsaicin (1 microM) produced similar inward currents in hVR1 transfected, but not in parental, HEK293 cells. These currents were abolished by capsazepine (1 microM). In the FLIPR anandamide and capsaicin were full agonists at hVR1, with pEC(50) values of 5. 94+/-0.06 (n=5) and 7.13+/-0.11 (n=8) respectively. The response to anandamide was inhibited by capsazepine (pK(B) of 7.40+/-0.02, n=6), but not by the cannabinoid receptor antagonists AM630 or AM281. Furthermore, pretreatment with capsaicin desensitized the anandamide-induced calcium response and vice versa. In conclusion, this study has demonstrated for the first time that anandamide acts as a full agonist at the human VR1.
通过基于荧光成像板读数器（FLIPR）的钙检测法筛选大量生物活性物质，内源性大麻素花生四烯乙醇胺被鉴定为重组人VR1（hVR1）的激动剂。进一步的电生理研究表明，花生四烯乙醇胺（10或100微摩尔）和辣椒素（1微摩尔）在转染了hVR1的HEK293细胞中产生相似的内向电流，但在未转染的亲本HEK293细胞中则不然。这些电流被辣椒平（1微摩尔）消除。在FLIPR实验中，花生四烯乙醇胺和辣椒素对hVR1都是完全激动剂，其pEC(50)值分别为5.94±0.06（n = 5）和7.13±0.11（n = 8）。花生四烯乙醇胺引起的反应被辣椒平抑制（pK(B)为7.40±0.02，n = 6），但不被大麻素受体拮抗剂AM630或AM281抑制。此外，用辣椒素预处理会使花生四烯乙醇胺诱导的钙反应脱敏，反之亦然。总之，本研究首次证明花生四烯乙醇胺在人VR1上作为完全激动剂起作用。
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