Anxiogenic-like effects induced by hemopressin in rats

Autor(es)

Fogaca, Manoela V. ^{[1, 2]} ; Sonego, Andreza B. ^{[1, 2]} ; Rioli, Vanessa ^[3] ; Gozzo, Fabio C. ^[4] ; Dale, Camila S. ^{[1, 5, 6]} ; Ferro, Emer S. ^{[1, 5, 6]} ; Guimaraes, Francisco S. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Butantan Inst, Ctr Toxins Immune Response & Cell Signaling CETIC, Special Lab Appl Toxinol LETA, BR-05503000 Sao Paulo, SP - Brazil

^[4] Univ Estadual Campinas, Inst Chem, BR-13083862 Campinas, SP - Brazil

^[5] Univ Sao Paulo, Biomed Sci Inst ICB, Dept Pharmacol, BR-05508000 Sao Paulo, SP - Brazil

^[6] Univ Sao Paulo, Ctr Interdisciplinary Res Interface Signaling Pro, BR-05508000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Pharmacology Biochemistry and Behavior; v. 129, p. 7-13, FEB 2015.
• Citações Web of Science: 14

Resumo

Hemopressin (PVNFKFLSH; HP) is an orally active peptide derived from rat hemoglobin alpha-chain that could act as an inverse agonist at cannabinoid type 1 receptors (CB1). Here, we aim to investigate possible behavioral effects of HP in male Wistar rats tested in the elevated plus maze (EPM), following HP intraperitoneal (i.p., 0.05 mg/kg), oral (P.O., 0.05 and 0.5 mg/kg) or intracerebroventricular (I.C.V., 3 and 10 nmol) administration. HP induced a decrease in EPM open arm exploration, indicating an anxiogenic-like effect. However, i.p. administration of HP (1 mg/kg) followed by mass spectrometry analysis of brain-peptide extracts suggested that the intact HP does not cross the blood brain barrier. I.C.V. administrated HP produced anxiogenic-like effects that were prevented by Transient Receptor Potential Vanilloid Type 1 (TRPV1) antagonists, 6-iodonordihydrocapsaicin (1 nmol) or SB366791 (1 nmol), but not by the CB1 receptor antagonist AM2S1 (0.1 and 1 nmol). Altogether, these data suggest that I.C.V. administrated HP induces anxiogenic-like effects by activating TRPV1 receptors. The similar anxiogenic effects observed after i.p. or P.O. administration could be due to HP fragment(s) crossing the blood brain barrier. The present results advance our knowledge about HP pharmacology and suggest concerns in future clinical studies. (C) 2014 Elsevier Inc All rights reserved. (AU)

• Processo FAPESP: 12/17626-7 - Mecanismos celulares e moleculares envolvidos no papel de neurotransmissores atípicos em transtornos neuropsiquiátricos
• Beneficiário: Francisco Silveira Guimaraes
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/50896-8 - Cannabidiol regulation of fear memory processing and associated brain function
• Beneficiário: Francisco Silveira Guimaraes
• Modalidade de apoio: Auxílio à Pesquisa - Regular