期刊
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
卷 129, 期 -, 页码 7-13出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2014.11.013
关键词
Endocannabinoids; Hemopressin; Anxiety; Cannabinoid; CB1 receptors; TRPV1 receptors
资金
- CNPq [470311/2012-6]
- FAPESP [2012/17626-7, 2012/50896-8]
- Pro-Reitoria de Pesquisa, University of Sao Paulo through Nucleo de Apoio a Pesquisa na Interface Proteolise-Sinalizacao Celular (NAPPS) [2012.1.17607.1.2]
- CNPq research fellowship
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [12/50896-8] Funding Source: FAPESP
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.
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