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Nongenomic Glucocorticoid Effects on Activity-Dependent Potentiation of Catecholamine Release in Chromaffin Cells

Department of Life Science (Y.-S.P., Y.H.C., C.-H.P., K.-T.K.), Division of Molecular and Life Sciences, Systems Biodynamics National Core Research Center, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea

Address all correspondence and requests for reprints to: Dr. Kyong-Tai Kim, Department of Life Science, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang 790-784, Republic of Korea. E-mail: ktk{at}postech.ac.kr.

Adrenal medulla chromaffin cells are neuroendocrine and modified sympathetic ganglion cells. Catecholamines released from chromaffin cells mediate the fight-or-flight response or alert reaction against dangerous conditions. Here we report that short-term treatment with glucocorticoids, released from adrenal cortex cells in response to chronic stress, inhibits activity-dependent potentiation (ADP) of catecholamine release. First, short-term treatment with dexamethasone (DEX), a synthetic glucocorticoid, reduces ADP in a concentration-dependent manner (IC₅₀ 324.2 ± 54.5 nM). The inhibitory effect of DEX is not reversed by RU-486 treatment, suggesting that the rapid inhibitory effect of DEX on ADP of catecholamine release is independent of glucocorticoid receptors. Second, DEX treatment reduces the frequency of fusion between vesicles and plasma membrane without affecting calcium influx. DEX disrupts activity-induced vesicle translocation and F-actin disassembly, thereby leading to inhibition of the vesicle fusion frequency. Third, we provide evidence that DEX reduces F-actin disassembly via inhibiting phosphorylation and translocation of myristoylated alanine-rich C kinase substrate and its upstream kinase protein kinase C. Altogether, we suggest that glucocorticoids inhibit ADP of catecholamine release by decreasing myristoylated alanine-rich C kinase substrate phosphorylation, which inhibits F-actin disassembly and vesicle translocation.