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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... 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. pKi values for displacement of [3H]‐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). pEC50 values for stimulating 45Ca2+ 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 (pEC50=7.37), a compound with the same substituted benzyl polar head group as arvanil. 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 (pKB=6.93 and 7.18 respectively) but were not antagonized by SR141716A (1 μM). Anandamide was less susceptible than capsaicin to antagonism by capsazepine (pKB=6.02) and less susceptible to antagonism by SR141716A (pKB=8.66) than methanandamide (pKB=9.56). WIN55212 was antagonized by SR141716A (pKB=9.02) but not by capsazepine (10 μM). 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

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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Publisher
Wiley
Copyright
"Copyright © 2001 Wiley Subscription Services, Inc., A Wiley Company"
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1038/sj.bjp.0703850
pmid
11159715
Publisher site
See Article on Publisher Site

Abstract

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. pKi values for displacement of [3H]‐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). pEC50 values for stimulating 45Ca2+ 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 (pEC50=7.37), a compound with the same substituted benzyl polar head group as arvanil. 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 (pKB=6.93 and 7.18 respectively) but were not antagonized by SR141716A (1 μM). Anandamide was less susceptible than capsaicin to antagonism by capsazepine (pKB=6.02) and less susceptible to antagonism by SR141716A (pKB=8.66) than methanandamide (pKB=9.56). WIN55212 was antagonized by SR141716A (pKB=9.02) but not by capsazepine (10 μM). 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.

Journal

British Journal of PharmacologyWiley

Published: Feb 1, 2001

Keywords: ; ; ; ; ; ; ; ; ;

References

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