HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Buy All Versions of this Article: fj.09-132142v1 23/9/3020    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gomes, I. Articles by Devi, L. A. Search for Related Content PubMed PubMed Citation Articles by Gomes, I. Articles by Devi, L. A.

Novel endogenous peptide agonists of cannabinoid receptors

Ivone Gomes^*, Julia S. Grushko, Urszula Golebiewska, Sascha Hoogendoorn^*, Achla Gupta^*, Andrea S. Heimann, Emer S. Ferro^||, Suzanne Scarlata, Lloyd D. Fricker and Lakshmi A. Devi^*,1

^* Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, New York, USA;

Department of Molecular Pharmacology, Albert Einstein College of Medicine, New York, New York, USA;

Department of Physiology and Biophysics, Stony Brook University Medical Center, Stony Brook, New York, USA;

Proteimax Biotechnology Ltd., Cotia, Brazil; and

^|| Department of Cell Biology and Development, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

¹ Correspondence: Department of Pharmacology and Systems Therapeutics, Mt. Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1603, New York, NY 10029, USA. E-mail: lakshmi.devi{at}mssm.edu

Hemopressin (Hp), a 9-residue -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) or two (VD-Hp) additional amino acids, as well as a β-hemoglobin-derived peptide with sequence similarity to that of hemopressin (VD-Hpβ). 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 and VD-Hp 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.—Gomes, I., Grushko, J. S., Golebiewska, U., Hoogendoorn, S., Gupta, A., Heimann, A. S., Ferro, E. S., Scarlata, S., Fricker, L. D., Devi, L. A. Novel endogenous peptide agonists of cannabinoid receptors.

Key Words: G-protein-coupled receptors • pain • analgesia • drug abuse

This article has been cited by other articles:

				Q. Liu, M. Bhat, W. D. Bowen, and J. Cheng Signaling Pathways from Cannabinoid Receptor-1 Activation to Inhibition of N-Methyl-D-Aspartic Acid Mediated Calcium Influx and Neurotoxicity in Dorsal Root Ganglion Neurons J. Pharmacol. Exp. Ther., December 1, 2009; 331(3): 1062 - 1070. [Abstract] [Full Text] [PDF]