Structure-activity relationship for the endogenous cannabinoid, anandamide, and certain of its analogues at vanilloid receptors in transfected cells and vas deferens

Ruth Alexandra Ross, Thomas Michael Gibson, H. C. Brockie, M. Leslie, G. Pashmi, Susan Craib, V. Di Marzo, Roger Guy Pertwee

Research output: Contribution to journalArticle

201 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)631-640
Number of pages9
JournalBritish Journal of Pharmacology
Volume132
Issue number3
DOIs
Publication statusPublished - Feb 2001

Keywords

  • anandamide
  • vanilloid
  • cannabinoid
  • VR1 transfected cells
  • structure-activity
  • mouse vas deferens
  • AM404
  • arvanil
  • capsaicin
  • RTX
  • CAPSAICIN
  • ANTAGONIST
  • CB1
  • PHARMACOLOGY
  • CAPSAZEPINE
  • INHIBITOR
  • LIGANDS

Cite this

Structure-activity relationship for the endogenous cannabinoid, anandamide, and certain of its analogues at vanilloid receptors in transfected cells and vas deferens. / Ross, Ruth Alexandra; Gibson, Thomas Michael; Brockie, H. C.; Leslie, M.; Pashmi, G.; Craib, Susan; Di Marzo, V.; Pertwee, Roger Guy.

In: British Journal of Pharmacology, Vol. 132, No. 3, 02.2001, p. 631-640.

Research output: Contribution to journalArticle

Ross, Ruth Alexandra ; Gibson, Thomas Michael ; Brockie, H. C. ; Leslie, M. ; Pashmi, G. ; Craib, Susan ; Di Marzo, V. ; Pertwee, Roger Guy. / Structure-activity relationship for the endogenous cannabinoid, anandamide, and certain of its analogues at vanilloid receptors in transfected cells and vas deferens. In: British Journal of Pharmacology. 2001 ; Vol. 132, No. 3. pp. 631-640.
@article{cf5ddc1e93b145dca261dc06598571ee,
title = "Structure-activity relationship for the endogenous cannabinoid, anandamide, and certain of its analogues at vanilloid receptors in transfected cells and vas deferens",
abstract = "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.",
keywords = "anandamide, vanilloid, cannabinoid, VR1 transfected cells, structure-activity, mouse vas deferens, AM404, arvanil, capsaicin, RTX, CAPSAICIN, ANTAGONIST, CB1, PHARMACOLOGY, CAPSAZEPINE, INHIBITOR, LIGANDS",
author = "Ross, {Ruth Alexandra} and Gibson, {Thomas Michael} and Brockie, {H. C.} and M. Leslie and G. Pashmi and Susan Craib and {Di Marzo}, V. and Pertwee, {Roger Guy}",
year = "2001",
month = "2",
doi = "10.1038/sj.bjp.0703850",
language = "English",
volume = "132",
pages = "631--640",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Structure-activity relationship for the endogenous cannabinoid, anandamide, and certain of its analogues at vanilloid receptors in transfected cells and vas deferens

AU - Ross, Ruth Alexandra

AU - Gibson, Thomas Michael

AU - Brockie, H. C.

AU - Leslie, M.

AU - Pashmi, G.

AU - Craib, Susan

AU - Di Marzo, V.

AU - Pertwee, Roger Guy

PY - 2001/2

Y1 - 2001/2

N2 - 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.

AB - 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.

KW - anandamide

KW - vanilloid

KW - cannabinoid

KW - VR1 transfected cells

KW - structure-activity

KW - mouse vas deferens

KW - AM404

KW - arvanil

KW - capsaicin

KW - RTX

KW - CAPSAICIN

KW - ANTAGONIST

KW - CB1

KW - PHARMACOLOGY

KW - CAPSAZEPINE

KW - INHIBITOR

KW - LIGANDS

U2 - 10.1038/sj.bjp.0703850

DO - 10.1038/sj.bjp.0703850

M3 - Article

VL - 132

SP - 631

EP - 640

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 3

ER -