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Endogenous cannabinoid receptor agonist anandamide induces peripheral antinociception by activation of ATP-sensitive K+ channels.
Life Sci. 2011 Apr 11; 88(15-16):653-7.LS

Abstract

AIMS

The effects of several potassium (K(+)) channel blockers were studied to determine which K(+) channels are involved in peripheral antinociception induced by the cannabinoid receptor agonist, anandamide.

MAIN METHODS

Hyperalgesia was induced by subcutaneous injection of 250 μg carrageenan into the plantar surface of the hind paw of rats. The extent of hyperalgesia was measured using a paw pressure test 3 h following carrageenan injection. The weight in grams (g) that elicited a nociceptive response, paw flexion, during the paw pressure test was used as the nociceptive response threshold.

KEY FINDINGS

Doses of 50, 75, and 100 ng of anandamide elicited a dose-dependent antinociceptive effect. Following a 100 ng dose of anandamide no antinociception was observed in the paw that was contralateral to the anandamide injection site, which shows that anandamide has a peripheral site of action. Pretreatment with 20, 40 and 80 μg AM251, a CB(1) receptor antagonist, caused a dose-dependent decrease in anandamide-induced antinociception, suggesting that the CB(1) receptor is directly involved in anandamide effect. Treatment with 40, 80 and 160 μg glibenclamide, an ATP-sensitive K(+) channel blocker, caused a dose-dependent reversal of anandamide-induced peripheral antinociception. Treatment with other K(+) channel antagonists, tetraethylammonium (30 μg), paxilline (10 μg) and dequalinium (50 μg), had no effect on the induction of peripheral antinociception by anandamide.

SIGNIFICANCE

This study provides evidence that the peripheral antinociceptive effect of the cannabinoid receptor agonist, anandamide, is primarily caused by activation of ATP-sensitive K(+) channels and does not involve other potassium channels.

Authors+Show Affiliations

Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31270-100, Belo Horizonte, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21277864

Citation

Reis, Gláucia Maria Lopes, et al. "Endogenous Cannabinoid Receptor Agonist Anandamide Induces Peripheral Antinociception By Activation of ATP-sensitive K+ Channels." Life Sciences, vol. 88, no. 15-16, 2011, pp. 653-7.
Reis GM, Ramos MA, Pacheco Dda F, et al. Endogenous cannabinoid receptor agonist anandamide induces peripheral antinociception by activation of ATP-sensitive K+ channels. Life Sci. 2011;88(15-16):653-7.
Reis, G. M., Ramos, M. A., Pacheco, D. d. a. . F., Klein, A., Perez, A. C., & Duarte, I. D. (2011). Endogenous cannabinoid receptor agonist anandamide induces peripheral antinociception by activation of ATP-sensitive K+ channels. Life Sciences, 88(15-16), 653-7. https://doi.org/10.1016/j.lfs.2011.01.017
Reis GM, et al. Endogenous Cannabinoid Receptor Agonist Anandamide Induces Peripheral Antinociception By Activation of ATP-sensitive K+ Channels. Life Sci. 2011 Apr 11;88(15-16):653-7. PubMed PMID: 21277864.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endogenous cannabinoid receptor agonist anandamide induces peripheral antinociception by activation of ATP-sensitive K+ channels. AU - Reis,Gláucia Maria Lopes, AU - Ramos,Marina Abadia, AU - Pacheco,Daniela da Fonseca, AU - Klein,André, AU - Perez,Andréa Castro, AU - Duarte,Igor Dimitri Gama, Y1 - 2011/01/26/ PY - 2010/07/21/received PY - 2010/12/15/revised PY - 2011/01/07/accepted PY - 2011/2/1/entrez PY - 2011/2/1/pubmed PY - 2011/6/1/medline SP - 653 EP - 7 JF - Life sciences JO - Life Sci VL - 88 IS - 15-16 N2 - AIMS: The effects of several potassium (K(+)) channel blockers were studied to determine which K(+) channels are involved in peripheral antinociception induced by the cannabinoid receptor agonist, anandamide. MAIN METHODS: Hyperalgesia was induced by subcutaneous injection of 250 μg carrageenan into the plantar surface of the hind paw of rats. The extent of hyperalgesia was measured using a paw pressure test 3 h following carrageenan injection. The weight in grams (g) that elicited a nociceptive response, paw flexion, during the paw pressure test was used as the nociceptive response threshold. KEY FINDINGS: Doses of 50, 75, and 100 ng of anandamide elicited a dose-dependent antinociceptive effect. Following a 100 ng dose of anandamide no antinociception was observed in the paw that was contralateral to the anandamide injection site, which shows that anandamide has a peripheral site of action. Pretreatment with 20, 40 and 80 μg AM251, a CB(1) receptor antagonist, caused a dose-dependent decrease in anandamide-induced antinociception, suggesting that the CB(1) receptor is directly involved in anandamide effect. Treatment with 40, 80 and 160 μg glibenclamide, an ATP-sensitive K(+) channel blocker, caused a dose-dependent reversal of anandamide-induced peripheral antinociception. Treatment with other K(+) channel antagonists, tetraethylammonium (30 μg), paxilline (10 μg) and dequalinium (50 μg), had no effect on the induction of peripheral antinociception by anandamide. SIGNIFICANCE: This study provides evidence that the peripheral antinociceptive effect of the cannabinoid receptor agonist, anandamide, is primarily caused by activation of ATP-sensitive K(+) channels and does not involve other potassium channels. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/21277864/Endogenous_cannabinoid_receptor_agonist_anandamide_induces_peripheral_antinociception_by_activation_of_ATP_sensitive_K+_channels_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(11)00037-3 DB - PRIME DP - Unbound Medicine ER -