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Human Brain Makes Its Own ‘Marijuana’

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U.S. and Brazilian scientists have discovered that the brain manufactures proteins that act like marijuana at specific receptors in the brain itself. This discovery may lead to new marijuana-like drugs for managing pain, stimulating appetite, and preventing marijuana abuse.

Scientists made their discovery by first extracting several small proteins, called peptides, from the brains of mice and determining their amino acid sequence. The extracted proteins were then compared with another peptide previously known to bind to, but not activate, the receptor (THC) affected by marijuana. Out of the extracted proteins, several not only bound to the brain’s THC receptors, but activated them as well.

The FASEB Journal Published online before print April 20, 2009 as doi: 10.1096/fj.09-132142.

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

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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 {alpha}-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.—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.

Written by huehueteotl

April 21, 2009 at 7:42 am

Posted in Neuroscience

One Response

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  1. very informative post, thank you indeed.

    Attitude Seeds

    September 12, 2010 at 6:02 am

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