Differential Responses of Genes for Neurosecretory Granules in the Rat Adrenal Medulla to Acute and Repeated Stress

Abstract

With acute stress, release of adrenomedullary catecholamines is important for handling the emergency situation. However, when chronic or repeated, stress leads to development or worsening of wide range of diseases. To clarify the mechanism, we studied changes in components of neurosecretory granules in adrenal medulla of male Sprague Dawley rats exposed to immobilization stress for 2 h once (1xIMO) or for 6 days (6xIMO). While vesicular monoamine transporter 1 (VMAT1) was expressed in all chromaffin cells, VMAT2, which has greater affinity for catecholamines, and higher turnover number than VMAT1, was expressed only in the NE‐cells under basal conditions. 1xIMO elevated VMAT2 mRNA, and after 6xIMO, this was reflected in nearly 3‐fold rise in VMAT2 protein, and expression in many Epi‐synthesizing cells. With 6xIMO, not only was VMAT2 mRNA still elevated, but chromogranin A (CgA) and chromogranin B (CgB) mRNAs were also increased 2–3 fold. The elevation of CgA, CgB and VMAT2 are each expected to increase the quantal size. This can facilitate more efficient use of the well characterized heightened catecholamine levels. To investigate a possible role of the HPA axis in induction of VMAT2, PC12 cells were treated with dexamethasone, which elevated VMAT2 mRNA expression. In contrast, the rise in Egr1 and P‐CREB may mediate the induction of CgA and CgB with repeated IMO stress.American Heart Association 10GRNT4420001