Down-regulation of 5-hydroxytryptamine7 receptors by dexamethasone in rat frontocortical astrocytes.
Astrocytes derived from rat frontal cortex contain 5-hydroxytryptamine7 (5-HT)7 receptors positively coupled to adenylyl cyclase. In the present study, we investigated the effects of glucocorticoids on adenylyl cyclase activity and 5-HT7 receptor gene expression in astrocytes. Addition of dexamethasone (0.01-100 nM, 12-72 h) to the culture medium decreased cyclic AMP formation induced by 5-HT in a time- and concentration-dependent manner. Dexamethasone treatment (10 nM, 48 h) reduced maximum responses of cyclic AMP formation induced by 5-HT and 5-carboxamidotryptamine without alterations in the EC50 value. In contrast, treatment with the mineralocorticoid aldosterone (48 h) had no significant effects on 5-HT-induced cyclic AMP formation with concentrations up to 10 nM. It was observed that dexamethasone treatment (1-100 nM, 3-72 h) also decreased the expression of 5-HT7 receptor mRNA, using reverse transcription and polymerase chain reaction analysis. A significant reduction in expression of 5-HT7 mRNA appeared at 3 h of dexamethasone treatment and reached a maximum at 6 h of treatment. On the other hand, dexamethasone treatment (10 nM, 48 h) did not affect basal levels of cyclic AMP and cyclic AMP synthesis stimulated by isoproterenol, N-ethylcarboxamidoadenosine, cholera toxin, and forskolin. These results suggest that dexamethasone decreases the expression of the 5-HT7 receptor gene and, consequently, 5-HT7 receptor-mediated signal transduction in frontocortical astrocytes.
Shimizu
M
M
Department of Psychiatry and Neuroscience, Institute of Clinical Research, Kure National Hospital, Japan.
Nishida
A
A
Zensho
H
H
Miyata
M
M
Yamawaki
S
S
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D005625:Frontal Lobe / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D005938:Glucocorticoids; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D014665:Vasodilator Agents; C104425:serotonin 7 receptor; D005576:Colforsin; D012701:Serotonin; D019830:Adenosine-5'-(N-ethylcarboxamide); D003907:Dexamethasone; D002772:Cholera Toxin; D000242:Cyclic AMP; D000241:Adenosine; D007545:Isoproterenol