Regulation of corticotropin-releasing factor receptor type 2 beta messenger ribonucleic acid in the rat cardiovascular system by urocortin, glucocorticoids, and cytokines.
CRF receptor type 2 (CRF R2) messenger RNA (mRNA) expression in the rodent heart is modulated by exposure to both the bacterial endotoxin lipopolysaccharide (LPS) and glucocorticoids. In this study we examined the roles of glucocorticoids, cytokines, and CRF R2beta ligands in the regulation of CRF R2beta expression in the cardiovascular system both in vivo and in vitro. Using ribonuclease protection assays, we found that, in addition to the injection of LPS or corticosterone, physical restraint caused a decrease in CRF R2beta mRNA levels in the rat heart and aorta. Adrenalectomy with corticosterone replacement at constant levels partially blocked LPS-induced decreases in CRF R2beta mRNA expression in the heart. Thus, elevations of endogenous circulating corticosterone could contribute to the down-regulation of CRF R2beta mRNA expression in heart. To identify other putative modulating factors, we examined CRF R2beta expression in the aorta-derived A7R5 cell line. Incubation with CRF R2 ligands or dexamethasone reduced CRF R2beta mRNA levels. In addition, incubation with a variety of cytokines, proteins released during immune challenge, also reduced CRF R2beta mRNA expression. The multifactorial regulation of CRF R2beta mRNA expression in the cardiovascular system may serve to limit the inotropic and chronotropic effects of CRF R2 agonists such as urocortin during prolonged physical or immune challenge.
Kageyama
K
K
The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037, USA.
Gaudriault
G E
GE
Bradbury
M J
MJ
Vale
W W
WW
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D002319:Cardiovascular System / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D012149:Restraint, Physical; D054832:Urocortins
D016207:Cytokines; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D020033:Protein Isoforms; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone