title: Anxiogenic-like effects induced by hemopressin in rats.
abstract: Hemopressin (PVNFKFLSH; HP) is an orally active peptide derived from rat hemoglobin α-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 AM251 (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.
authors.affiliation: Department of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil. Electronic address: manoelafogaca@usp.br.
authors.forename: Manoela V
authors.initials: MV
authors.lastname: Fogaça
authors.affiliation: Department of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.
authors.forename: Andreza B
authors.initials: AB
authors.lastname: Sonego
authors.affiliation: Special Laboratory of Applied Toxinology (LETA), Center of Toxins, Immune Response and Cell Signaling (CETICS), Butantan Institute, 05503-000 São Paulo, SP, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Rioli
authors.affiliation: Institute of Chemistry, State University of Campinas, 13083-862 Campinas, SP, Brazil.
authors.forename: Fabio C
authors.initials: FC
authors.lastname: Gozzo
authors.affiliation: Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil; Department of Pharmacology, Biomedical Sciences Institute (ICB), University of São Paulo (USP), São Paulo 05508-000, SP, Brazil; Center for Interdisciplinary Research on Interface Signaling-Proteolyses (NAPPS), University of São Paulo, Brazil.
authors.forename: Camila S
authors.initials: CS
authors.lastname: Dale
authors.affiliation: Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil; Department of Pharmacology, Biomedical Sciences Institute (ICB), University of São Paulo (USP), São Paulo 05508-000, SP, Brazil; Center for Interdisciplinary Research on Interface Signaling-Proteolyses (NAPPS), University of São Paulo, Brazil.
authors.forename: Emer S
authors.initials: ES
authors.lastname: Ferro
authors.affiliation: Department of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Guimarães
mesh_terms: D000813:Anilides / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D001921:Brain / Q000378:metabolism; D002211:Capsaicin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D002934:Cinnamates / Q000008:administration & dosage / Q000494:pharmacology; D006454:Hemoglobins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: C576177:6-iodonordihydrocapsaicin; D000813:Anilides; D002934:Cinnamates; D006454:Hemoglobins; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D010446:Peptide Fragments; D010880:Piperidines; D011720:Pyrazoles; C473218:hemopressin; C103505:AM 251; D002211:Capsaicin
keywords: Anxiety; CB(1) receptors; Cannabinoid; Endocannabinoids; Hemopressin; TRPV(1) receptors