| Full text | |
| Author(s): |
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]
Total Authors: 10
|
| Affiliation: | [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
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | FASEB JOURNAL; v. 23, n. 9, p. 3020-3029, Sept. 2009. |
| Field of knowledge: | Biological Sciences - Morphology |
| Web of Science Citations: | 86 |
| Abstract | |
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) | |
| FAPESP's process: | 04/14258-0 - Conformation-specific antibodies: proposal for generation of antibodies directed at receptors linked to active G protein (GPCRs) |
| Grantee: | Andrea Sterman Heimann |
| Support Opportunities: | Research Grants - Innovative Research in Small Business - PIPE |
| FAPESP's process: | 04/04933-2 - Molecular cell biology of oligopeptidases |
| Grantee: | Emer Suavinho Ferro |
| Support Opportunities: | Research Projects - Thematic Grants |