The serotonin transporter is required for stress-evoked increases in adrenal catecholamine synthesis and angiotensin II AT(2) receptor expression.
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 AT(2) receptor expression. There are no alterations in adrenal catecholamine content during restraint. In littermate 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 AT(2) 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 AT(2) receptors in catecholamine synthesis and release during stress.
Section on Pharmacology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1514, USA. ArmandoI@intra.nimh.nih.gov
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Armando
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Tjurmina
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Li
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Murphy
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Saavedra
D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002395:Catecholamines / Q000096:biosynthesis* / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism*; D012149:Restraint, Physical / Q000379:methods; D050486:Serotonin Plasma Membrane Transport Proteins; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D002395:Catecholamines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D011945:Receptors, Angiotensin; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine