Busca avançada
Ano de início
Entree
(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.)

Novel endogenous peptide agonists of cannabinoid receptors

Texto completo
Autor(es):
Gomes, Ivone [1] ; Grushko, Julia S. [2] ; Golebiewska, Urszula [3] ; Hoogendoorn, Sascha [1] ; Gupta, Achla [1] ; Heimann, Andrea S. [4] ; Ferro, Emer S. [5] ; Scarlata, Suzanne [3] ; Fricker, Lloyd D. [2] ; Devi, Lakshmi A. [1]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 - USA
[2] Albert Einstein Coll Med, Dept Mol Pharmacol, New York, NY - USA
[3] SUNY Stony Brook, Dept Physiol & Biophys, Med Ctr, New York, NY - USA
[4] Proteimax Biotechnol Ltd, Cotia - Brazil
[5] Univ Sao Paulo, Dept Cell Biol & Dev, Inst Biomed Sci, Sao Paulo - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: FASEB JOURNAL; v. 23, n. 9, p. 3020-3029, Sept. 2009.
Área do conhecimento: Ciências Biológicas - Morfologia
Citações Web of Science: 86
Assunto(s):Analgesia   Transtornos relacionados ao uso de substâncias   Receptores de canabinóides   Proteína quinase 3 ativada por mitógeno   Condições patológicas, sinais e sintomas   Dor
Resumo

Hemopressin (Hp), a 9-residue alpha-hemoglobin-derived peptide, was previously reported to function as a CB1 cannabinoid receptor antagonist (1) . In this study, we report that mass spectrometry (MS) data from peptidomics analyses of mouse brain extracts identified N-terminally extended forms of Hp containing either three (RVD-Hp-alpha) or two (VD-Hp-alpha) additional amino acids, as well as a beta-hemoglobin-derived peptide with sequence similarity to that of hemopressin (VD-Hp-beta). Characterization of the -hemoglobin-derived peptides using binding and functional assays shows that in contrast to Hp, which functions as a CB1 cannabinoid receptor antagonist, both RVD-Hp-alpha and VD-Hp-alpha function as agonists. Studies examining the increase in the phosphorylation of ERK1/2 levels or release of intracellular Ca2+ indicate that these peptides activate a signal transduction pathway distinct from that activated by the endocannabinoid, 2-arachidonoylglycerol, or the classic CB1 agonist, Hu-210. This finding suggests an additional mode of regulation of endogenous cannabinoid receptor activity. Taken together, these results suggest that the CB1 receptor is involved in the integration of signals from both lipid- and peptide-derived signaling molecules. (AU)

Processo FAPESP: 04/04933-2 - Biologia celular molecular de oligopeptidases
Beneficiário:Emer Suavinho Ferro
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 04/14258-0 - Anticorpos conformação específicos: proposta para geração de anticorpos dirigidos a receptores acoplados à proteina G (GPCRs) ativados
Beneficiário:Andrea Sterman Heimann
Linha de fomento: Auxílio à Pesquisa - Pesquisa Inovativa em Pequenas Empresas - PIPE