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Study of the involvement of K+ channels in the peripheral antinociception of the kappa-opioid receptor agonist bremazocine.
Eur J Pharmacol. 2004 Jun 28; 494(2-3):155-60.EJ

Abstract

The involvement of the nitric oxide (NO)/cyclic GMP pathway in the molecular mechanisms of antinociceptive drugs like morphine has been previously shown by our group. Additionally, it is known that the desensitisation of nociceptors by K(+) channel opening should be the final target for several analgesic drugs including nitric oxide donors and exogenous micro-opioid receptor agonists. In our previous study, we demonstrated that bremazocine, a kappa-opioid receptor agonist, induces peripheral antinociception by activating nitric oxide/cyclic GMP pathway. In the current study, we assessed whether bremazocine is capable to activate K(+) channels eliciting antinociception. Bremazocine (20, 40 and 50 microg) dose-dependently reversed the hyperalgesia induced in the rat paw by local injection of carrageenan (250 microg) or prostaglandin E(2) (2 microg), measured by the paw pressure test. Using the selective kappa-opioid receptor antagonist nor-binaltorphimine (Nor-BNI, 200 microg/paw), it was confirmed that bremazocine (50 microg/paw) acts specifically on the kappa-opioid receptors present at peripheral sites. Prior treatment with the ATP-sensitive K(+) channel blockers glibenclamide (40, 80 and 160 microg) and tolbutamide (40, 80 and 160 microg) did not antagonise the antinociceptive effect of bremazocine (50 microg). The same results were obtained when we used prostaglandin E(2) (2 microg) as the hyperalgesic stimulus. The supposed participation of other types of K(+) channels was tested using the Ca(2+)-activated K(+) channel blockers dequalinium (12.5, 25 and 50 microg) and charybdotoxin (0.5, 1 and 2 microg) and different types of the non-selective K(+) channel blockers tetraethylammonium (25, 50 and 100 microg) and 4-aminopyridine (10, 25 and 50 microg). None of the K(+) channel blockers reversed the antinociceptive effect of bremazocine. On the basis of these results, we suggest that K(+) channels are not involved in the peripheral antinociceptive effect of bremazocine, although this opioid receptor agonist induces nitric oxide/cGMP pathway activation.

Authors+Show Affiliations

Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos 6627, Belo Horizonte MG, 31.270-100, Brazil.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15212969

Citation

Amarante, Luiz H., et al. "Study of the Involvement of K+ Channels in the Peripheral Antinociception of the Kappa-opioid Receptor Agonist Bremazocine." European Journal of Pharmacology, vol. 494, no. 2-3, 2004, pp. 155-60.
Amarante LH, Alves DP, Duarte ID. Study of the involvement of K+ channels in the peripheral antinociception of the kappa-opioid receptor agonist bremazocine. Eur J Pharmacol. 2004;494(2-3):155-60.
Amarante, L. H., Alves, D. P., & Duarte, I. D. (2004). Study of the involvement of K+ channels in the peripheral antinociception of the kappa-opioid receptor agonist bremazocine. European Journal of Pharmacology, 494(2-3), 155-60.
Amarante LH, Alves DP, Duarte ID. Study of the Involvement of K+ Channels in the Peripheral Antinociception of the Kappa-opioid Receptor Agonist Bremazocine. Eur J Pharmacol. 2004 Jun 28;494(2-3):155-60. PubMed PMID: 15212969.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Study of the involvement of K+ channels in the peripheral antinociception of the kappa-opioid receptor agonist bremazocine. AU - Amarante,Luiz H, AU - Alves,Daniela P, AU - Duarte,Igor D G, PY - 2003/12/22/received PY - 2004/04/19/revised PY - 2004/05/10/accepted PY - 2004/6/24/pubmed PY - 2005/2/16/medline PY - 2004/6/24/entrez SP - 155 EP - 60 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 494 IS - 2-3 N2 - The involvement of the nitric oxide (NO)/cyclic GMP pathway in the molecular mechanisms of antinociceptive drugs like morphine has been previously shown by our group. Additionally, it is known that the desensitisation of nociceptors by K(+) channel opening should be the final target for several analgesic drugs including nitric oxide donors and exogenous micro-opioid receptor agonists. In our previous study, we demonstrated that bremazocine, a kappa-opioid receptor agonist, induces peripheral antinociception by activating nitric oxide/cyclic GMP pathway. In the current study, we assessed whether bremazocine is capable to activate K(+) channels eliciting antinociception. Bremazocine (20, 40 and 50 microg) dose-dependently reversed the hyperalgesia induced in the rat paw by local injection of carrageenan (250 microg) or prostaglandin E(2) (2 microg), measured by the paw pressure test. Using the selective kappa-opioid receptor antagonist nor-binaltorphimine (Nor-BNI, 200 microg/paw), it was confirmed that bremazocine (50 microg/paw) acts specifically on the kappa-opioid receptors present at peripheral sites. Prior treatment with the ATP-sensitive K(+) channel blockers glibenclamide (40, 80 and 160 microg) and tolbutamide (40, 80 and 160 microg) did not antagonise the antinociceptive effect of bremazocine (50 microg). The same results were obtained when we used prostaglandin E(2) (2 microg) as the hyperalgesic stimulus. The supposed participation of other types of K(+) channels was tested using the Ca(2+)-activated K(+) channel blockers dequalinium (12.5, 25 and 50 microg) and charybdotoxin (0.5, 1 and 2 microg) and different types of the non-selective K(+) channel blockers tetraethylammonium (25, 50 and 100 microg) and 4-aminopyridine (10, 25 and 50 microg). None of the K(+) channel blockers reversed the antinociceptive effect of bremazocine. On the basis of these results, we suggest that K(+) channels are not involved in the peripheral antinociceptive effect of bremazocine, although this opioid receptor agonist induces nitric oxide/cGMP pathway activation. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/15212969/Study_of_the_involvement_of_K+_channels_in_the_peripheral_antinociception_of_the_kappa_opioid_receptor_agonist_bremazocine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014299904005035 DB - PRIME DP - Unbound Medicine ER -