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

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