The serotonin transporter is required for stress-evoked increases in adrenal catecholamine synthesis and angiotensin II AT2 receptor expression

Document Type

Journal Article

Publication Date

11-24-2003

Journal

Neuroendocrinology

Volume

78

Issue

4

DOI

10.1159/000073705

Keywords

Adrenal medulla; Angiotensin receptors; Angiotensins; Catecholamines; In situ hybridization; Serotonin; Serotonin transporter; Stress; Tyrosine hydroxylase

Abstract

High numbers of serotonin transporter (SERT) binding sites and high serotonin (5-HT) content are expressed in the adrenal medulla of wild-type (SERT+/+) mice. Acute restraint stress increases adrenomedullary 5-HT, norepinephrine (NE) and epinephrine (E) release, adrenomedullary tyrosine hydroxylase (TH) mRNA, and angiotensin II AT2 receptor expression. There are no alterations in adrenal catecholamine content during restraint. In litter-mate SERT-/- mice, which do not express SERT binding sites, the basal adrenomedullary 5-HT content is significantly reduced and does not increase after stress. The stress-induced increase in plasma E is higher in SERT-/- than in SERT+/+ animals. In SERT-/- mice, the stress-induced increase in expression of TH mRNA does not occur, and as a consequence, adrenal E content decreases, and adrenal E and NE content are lower than that of SERT+/+ mice during restraint. In addition, instead of increased expression, stress induces a profound decrease in the number of adrenomedullary AT2 receptors in SERT-/- mice. Our results indicate that SERT is necessary for the stress-induced increase in adrenomedullary catecholamine synthesis and AT 2 receptor expression. These data further indicate a close relationship between the adrenomedullary 5-HT and angiotensin II systems, and an important role of adrenomedullary AT2 receptors in catecholamine synthesis and release during stress. Copyright © 2003 S. Karger AG, Basel.

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