A possible role of lipoxygenase in the activation of vanilloid receptors by anandamide in the guinea-pig bronchus

Susan Craib, H. C. Ellington, Roger Guy Pertwee, Ruth Alexandra Ross

Research output: Contribution to journalArticle

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Abstract

1 In the absence of indomethacin, anandamide did not contract the guinea-pig bronchus at concentrations up to 100 muM. In the presence of indomethacin (10 muM), anandamide induced concentration-related contractions with a pEC(50) value of 5.18 +/-0.11. It was significantly less potent than capsaicin (pEC(50) 7.01 +/-0.1). The anandamide uptake inhibitor AM404, produced only a 14.1 +/-3.22% contraction at 100 muM. All experiments were conducted in the presence of PMSF (20 muM).

2 The vanilloid receptor antagonist. capsazepine (10 muM), significantly attenuated the contractile effect of anandamide. the response to 100 pm anandamide being 40.53 +/-7.04% in the presence of vehicle and 1.57 +/-8.93% in the presence of 10 muM capsazepine. The contractile actions of anandamide and AM404 were markedly enhanced by the peptidase inhibitor thiorphan.

3 The log concentration-response curve of anandamide was unaltered by the CB1 receptor antagonist, SR141716A. The pEC(50) values for anandamide were 4.88 +/-0.08 and 5.17 +/-0.19 in the presence of vehicle and SR141716A (I pm) respectively.

4 The lipoxygenase inhibitors 5,8,11,14-eicosatetraynoic acid (ETYA) and 5,8,11 eicosatriynoic acid (ETI) reduced the effect of 100 muM anandamide from 34.7 +/-1.9% (vehicle) to 7.7 +/-5% (ETYA, 10 pm) and from 41.85 +/-4.25% (n=6) (vehicle) to 10.31 +/-3.54 (n=6) (ETI, 20 muM). Neither inhibitor significantly affected contraction of the tissue by substance P.

5 This study provides evidence that anandamide acts on vanilloid receptors in the guinea-pig isolated bronchus. These data raise the possibility that the contractile action of anandamide may be due, at least in part, to lipoxygenase metabolites of this fatty acid amide that are vanilloid receptor agonists.

Original languageEnglish
Pages (from-to)30-37
Number of pages7
JournalBritish Journal of Pharmacology
Volume134
Issue number1
DOIs
Publication statusPublished - Sep 2001

Keywords

  • anandamide
  • bronchus
  • vanilloid
  • cannabinoid
  • lipoxygenase
  • cyclooxygenase
  • ETYA
  • ETI
  • cpasaicin receptors
  • cannabinoids
  • acid
  • metabolism
  • mechanisms
  • nerves

Cite this

A possible role of lipoxygenase in the activation of vanilloid receptors by anandamide in the guinea-pig bronchus. / Craib, Susan; Ellington, H. C.; Pertwee, Roger Guy; Ross, Ruth Alexandra.

In: British Journal of Pharmacology, Vol. 134, No. 1, 09.2001, p. 30-37.

Research output: Contribution to journalArticle

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abstract = "1 In the absence of indomethacin, anandamide did not contract the guinea-pig bronchus at concentrations up to 100 muM. In the presence of indomethacin (10 muM), anandamide induced concentration-related contractions with a pEC(50) value of 5.18 +/-0.11. It was significantly less potent than capsaicin (pEC(50) 7.01 +/-0.1). The anandamide uptake inhibitor AM404, produced only a 14.1 +/-3.22{\%} contraction at 100 muM. All experiments were conducted in the presence of PMSF (20 muM).2 The vanilloid receptor antagonist. capsazepine (10 muM), significantly attenuated the contractile effect of anandamide. the response to 100 pm anandamide being 40.53 +/-7.04{\%} in the presence of vehicle and 1.57 +/-8.93{\%} in the presence of 10 muM capsazepine. The contractile actions of anandamide and AM404 were markedly enhanced by the peptidase inhibitor thiorphan.3 The log concentration-response curve of anandamide was unaltered by the CB1 receptor antagonist, SR141716A. The pEC(50) values for anandamide were 4.88 +/-0.08 and 5.17 +/-0.19 in the presence of vehicle and SR141716A (I pm) respectively.4 The lipoxygenase inhibitors 5,8,11,14-eicosatetraynoic acid (ETYA) and 5,8,11 eicosatriynoic acid (ETI) reduced the effect of 100 muM anandamide from 34.7 +/-1.9{\%} (vehicle) to 7.7 +/-5{\%} (ETYA, 10 pm) and from 41.85 +/-4.25{\%} (n=6) (vehicle) to 10.31 +/-3.54 (n=6) (ETI, 20 muM). Neither inhibitor significantly affected contraction of the tissue by substance P.5 This study provides evidence that anandamide acts on vanilloid receptors in the guinea-pig isolated bronchus. These data raise the possibility that the contractile action of anandamide may be due, at least in part, to lipoxygenase metabolites of this fatty acid amide that are vanilloid receptor agonists.",
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T1 - A possible role of lipoxygenase in the activation of vanilloid receptors by anandamide in the guinea-pig bronchus

AU - Craib, Susan

AU - Ellington, H. C.

AU - Pertwee, Roger Guy

AU - Ross, Ruth Alexandra

PY - 2001/9

Y1 - 2001/9

N2 - 1 In the absence of indomethacin, anandamide did not contract the guinea-pig bronchus at concentrations up to 100 muM. In the presence of indomethacin (10 muM), anandamide induced concentration-related contractions with a pEC(50) value of 5.18 +/-0.11. It was significantly less potent than capsaicin (pEC(50) 7.01 +/-0.1). The anandamide uptake inhibitor AM404, produced only a 14.1 +/-3.22% contraction at 100 muM. All experiments were conducted in the presence of PMSF (20 muM).2 The vanilloid receptor antagonist. capsazepine (10 muM), significantly attenuated the contractile effect of anandamide. the response to 100 pm anandamide being 40.53 +/-7.04% in the presence of vehicle and 1.57 +/-8.93% in the presence of 10 muM capsazepine. The contractile actions of anandamide and AM404 were markedly enhanced by the peptidase inhibitor thiorphan.3 The log concentration-response curve of anandamide was unaltered by the CB1 receptor antagonist, SR141716A. The pEC(50) values for anandamide were 4.88 +/-0.08 and 5.17 +/-0.19 in the presence of vehicle and SR141716A (I pm) respectively.4 The lipoxygenase inhibitors 5,8,11,14-eicosatetraynoic acid (ETYA) and 5,8,11 eicosatriynoic acid (ETI) reduced the effect of 100 muM anandamide from 34.7 +/-1.9% (vehicle) to 7.7 +/-5% (ETYA, 10 pm) and from 41.85 +/-4.25% (n=6) (vehicle) to 10.31 +/-3.54 (n=6) (ETI, 20 muM). Neither inhibitor significantly affected contraction of the tissue by substance P.5 This study provides evidence that anandamide acts on vanilloid receptors in the guinea-pig isolated bronchus. These data raise the possibility that the contractile action of anandamide may be due, at least in part, to lipoxygenase metabolites of this fatty acid amide that are vanilloid receptor agonists.

AB - 1 In the absence of indomethacin, anandamide did not contract the guinea-pig bronchus at concentrations up to 100 muM. In the presence of indomethacin (10 muM), anandamide induced concentration-related contractions with a pEC(50) value of 5.18 +/-0.11. It was significantly less potent than capsaicin (pEC(50) 7.01 +/-0.1). The anandamide uptake inhibitor AM404, produced only a 14.1 +/-3.22% contraction at 100 muM. All experiments were conducted in the presence of PMSF (20 muM).2 The vanilloid receptor antagonist. capsazepine (10 muM), significantly attenuated the contractile effect of anandamide. the response to 100 pm anandamide being 40.53 +/-7.04% in the presence of vehicle and 1.57 +/-8.93% in the presence of 10 muM capsazepine. The contractile actions of anandamide and AM404 were markedly enhanced by the peptidase inhibitor thiorphan.3 The log concentration-response curve of anandamide was unaltered by the CB1 receptor antagonist, SR141716A. The pEC(50) values for anandamide were 4.88 +/-0.08 and 5.17 +/-0.19 in the presence of vehicle and SR141716A (I pm) respectively.4 The lipoxygenase inhibitors 5,8,11,14-eicosatetraynoic acid (ETYA) and 5,8,11 eicosatriynoic acid (ETI) reduced the effect of 100 muM anandamide from 34.7 +/-1.9% (vehicle) to 7.7 +/-5% (ETYA, 10 pm) and from 41.85 +/-4.25% (n=6) (vehicle) to 10.31 +/-3.54 (n=6) (ETI, 20 muM). Neither inhibitor significantly affected contraction of the tissue by substance P.5 This study provides evidence that anandamide acts on vanilloid receptors in the guinea-pig isolated bronchus. These data raise the possibility that the contractile action of anandamide may be due, at least in part, to lipoxygenase metabolites of this fatty acid amide that are vanilloid receptor agonists.

KW - anandamide

KW - bronchus

KW - vanilloid

KW - cannabinoid

KW - lipoxygenase

KW - cyclooxygenase

KW - ETYA

KW - ETI

KW - cpasaicin receptors

KW - cannabinoids

KW - acid

KW - metabolism

KW - mechanisms

KW - nerves

U2 - 10.1038/sj.bjp.0704223

DO - 10.1038/sj.bjp.0704223

M3 - Article

VL - 134

SP - 30

EP - 37

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 1

ER -