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.
Armando
I
I
Section on Pharmacology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1514, USA. ArmandoI@intra.nimh.nih.gov
Tjurmina
O A
OA
Li
Q
Q
Murphy
D L
DL
Saavedra
J M
JM
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