Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla.

Hofer Reyes, Stefanie; Ralvenius, William T; Gachet Otanez, Maria Salomé; Fritschy, Jean-Marc; Zeilhofer, Ulrich; Gertsch, Jürg (2015). Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla. Neuropharmacology, 98, pp. 78-89. Elsevier 10.1016/j.neuropharm.2015.03.021

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The endocannabinoid system (ECS) comprises the cannabinoid receptors CB1 and CB2 and their endogenous arachidonic acid-derived agonists 2-arachidonoyl glycerol and anandamide, which play important neuromodulatory roles. Recently, a novel class of negative allosteric CB1 receptor peptide ligands, hemopressin-like peptides derived from alpha hemoglobin, has been described, with yet unknown origin and function in the CNS. Using monoclonal antibodies we now identified the localization of RVD-hemopressin (pepcan-12) and N-terminally extended peptide endocannabinoids (pepcans) in the CNS and determined their neuronal origin. Immunohistochemical analyses in rodents revealed distinctive and specific staining in major groups of noradrenergic neurons, including the locus coeruleus (LC), A1, A5 and A7 neurons, which appear to be major sites of production/release in the CNS. No staining was detected in dopaminergic neurons. Peptidergic axons were seen throughout the brain (notably hippocampus and cerebral cortex) and spinal cord, indicative of anterograde axonal transport of pepcans. Intriguingly, the chromaffin cells in the adrenal medulla were also strongly stained for pepcans. We found specific co-expression of pepcans with galanin, both in the LC and adrenal gland. Using LC-MS/MS, pepcan-12 was only detected in non-perfused brain (∼40 pmol/g), suggesting that in the CNS it is secreted and present in extracellular compartments. In adrenal glands, significantly more pepcan-12 (400-700 pmol/g) was measured in both non-perfused and perfused tissue. Thus, chromaffin cells may be a major production site of pepcan-12 found in blood. These data uncover important areas of peptide endocannabinoid occurrence with exclusive noradrenergic immunohistochemical staining, opening new doors to investigate their potential physiological function in the ECS. This article is part of a Special Issue entitled 'Fluorescent Neuro-Ligands'.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Hofer Reyes, Stefanie; Gachet Otanez, Maria Salomé and Gertsch, Jürg

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0028-3908

Publisher:

Elsevier

Language:

English

Submitter:

Kevin Marc Rupp

Date Deposited:

18 May 2015 16:52

Last Modified:

26 Jun 2016 02:02

Publisher DOI:

10.1016/j.neuropharm.2015.03.021

PubMed ID:

25839900

Uncontrolled Keywords:

Adrenal gland; CB1 receptor; Hemopressin; Locus coeruleus; Neuropeptides; Noradrenergic system; Pepcan-12; Pepcans

BORIS DOI:

10.7892/boris.68422

URI:

https://boris.unibe.ch/id/eprint/68422

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