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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Peripheral interactions between cannabinoid and opioid systems contribute to the antinociceptive effect of crotalphine

Texto completo
Autor(es):
Machado, F. C. [1, 2] ; Zambelli, V. O. [2] ; Fernandes, A. C. O. [2] ; Heimann, A. S. [3] ; Cury, Y. [2] ; Picolo, G. [2]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Ciencias Biomed, BR-05508 Sao Paulo - Brazil
[2] Inst Butantan, Lab Especial Dor & Sinalizacao, BR-05503900 Sao Paulo - Brazil
[3] Proteimax Biotechnol, Cotia - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: British Journal of Pharmacology; v. 171, n. 4, SI, p. 961-972, FEB 2014.
Citações Web of Science: 19
Resumo

Background and Purpose Crotalphine is an antinociceptive peptide that, despite its opioid-like activity, does not induce some of the characteristic side effects of opioids, and its amino acid sequence has no homology to any known opioid peptide. Here, we evaluated the involvement of the peripheral cannabinoid system in the crotalphine effect and its interaction with the opioid system. Experimental Approach Hyperalgesia was evaluated using the rat paw pressure test. Involvement of the cannabinoid system was determined using a selective cannabinoid receptor antagonist. Cannabinoid and opioid receptor activation were evaluated in paw slices by immunofluorescence assays using conformation state-sensitive antibodies. The release of endogenous opioid peptides from skin tissue was measured using a commercial enzyme immunoassay (EIA). Key Results Both p.o. (0.008-1.0 mu g.kg(-1)) and intraplantar (0.0006 mu g per paw) administration of crotalphine induced antinociception in PGE(2)-induced hyperalgesia. Antinociception by p.o. crotalphine (1 mu g.kg(-1)) was blocked by AM630 (50 mu g per paw), a CB2 receptor antagonist, and by antiserum anti-dynorphin A (1 mu g per paw). Immunoassay studies confirmed that crotalphine increased the activation of both kappa-opioid (51.7%) and CB2 (28.5%) receptors in paw tissue. The local release of dynorphin A from paw skin was confirmed by in vitro EIA and blocked by AM630. Conclusions and Implications Crotalphine-induced antinociception involves peripheral CB2 cannabinoid receptors and local release of dynorphin A, which is dependent on CB2 receptor activation. These results enhance our understanding of the mechanisms involved in the peripheral effect of crotalphine, as well as the interaction between the opioid and cannabinoid systems. (AU)

Processo FAPESP: 09/14203-5 - Avaliação da participação de receptores canabinóides no efeito antinociceptivo da crotalfina, um analgésico tipo opióide, e sua interação com o sistema opióide
Beneficiário:Gisele Picolo
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 10/12917-8 - Contribuição do sistema canabinóide e sua interação com o sistema opióide na antinocicepção induzida pela crotalfina, um analgésico tipo opióide
Beneficiário:Franciele Corrêa Machado
Linha de fomento: Bolsas no Brasil - Mestrado
Processo FAPESP: 08/57898-0 - Instituto Nacional de Ciência e Tecnologia em Toxinas
Beneficiário:Osvaldo Augusto Brazil Esteves Sant'Anna
Linha de fomento: Auxílio à Pesquisa - Temático