Chemerin Peptide Releases Catecholamines from Rat Adrenal Medulla

Background: Chemerin is an adipokine typically known for its role in inflammation. Recent studies suggest that it plays a part in the development of obesity and hypertension. Because of the importance of the sympathetic nervous system in blood pressure control and because the adrenal is an important effector of this system, we hypothesized that chemerin would be present in the adrenal glands and would release catecholamines through activation of its main receptor, chemokine like receptor 1 (CMKLR1, ChemR23). Methodology: Immunohistochemistry was used to assess the presence of chemerin and two of its receptors, CMKLR1 and G protein coupled receptor 1 (GPR1), in isolated whole adrenal glands from normal male, Sprague Dawley rats. There was a moderate level of chemerin expression in the medulla and the cortex. The CMKLR1 expression was moderate in the cortex and absent in the medullae. By contrast, a robust level of GPR1 in the cortex and medulla was observed. High-pressure liquid chromatography (HPLC) was used to measure the amount of norepinephrine and epinephrine released by the adrenal medullae when incubated in vitro with a stimulus. Results: Chemerin-9 (100 nM, a shorter and stable chemerin analog) caused a significant 90.0±24.0% increase of norepinephrine and a 69.0±3.4% increase of epinephrine vs vehicle paired adrenal medullae. However, the CMKLR1 antagonist CCX832 did not block chemerin-9 induced release of catecholamines from the medulla. Conclusion: These data are the first to suggest that chemerin may have a function within the adrenal, causing active release of catecholamines, an action that would support an elevation in blood pressure.