Posttranscriptional mechanisms contribute to osmotic regulation of ANG type 1 receptors in cultured rat renomedullary interstitial cells.
Am J Physiol Regul Integr Comp Physiol
; 290(1): R44-9, 2006 Jan.
Article
de En
| MEDLINE
| ID: mdl-16099820
ABSTRACT
Previously, we showed that ANG II receptors in cultured rat renomedullary interstitial cells (RMICs) are osmotically regulated (19). The current study examined the mechanisms underlying this osmotic regulation in RMICs cultured in isoosmotic (300 mosmol/kgH2O) and hyperosmotic (600 mosmol/kgH2O) conditions. Radioligand competition analysis coupled with RNase protection assays (RPA) and ligand-mediated receptor internalization studies revealed that RMICs primarily express the type 1a angiotensin receptor (AT(1a)R). When cultured under hyperosmotic conditions, the density (B(max)) of AT1R in RMIC membranes decreased by 31% [B(max) (pmol/mg protein) 300 mosmol/kgH2O, 6.44 +/- 0.46 vs. 600 mosmol/kgH2O, 4.42 +/- 0.37, n = 8, P < 0.01], under conditions in which no detectable changes in AT(1a)R mRNA expression or in the kinetics of ligand-mediated AT1R internalization were observed. RNA electromobility shift assays showed that RNA protein complex (RPC) formation between RMIC cytosolic RNA binding proteins and the 5' leader sequence (5'LS) of the AT(1a)R was increased 1.5-fold under hyperosmotic conditions [5'LS RPC (arbitrary units) 300 mosmol/kgH2O, 0.79 +/- 0.08 vs. 600 mosmol/kgH2O, 1.17 +/- 0.07, n = 4, P < 0.01]. These results suggest that the downregulation of AT(1a)R expression in RMICs cultured under hyperosmotic conditions is regulated at the posttranscriptional level by RNA binding proteins that interact within the 5'LS of the AT(1a)R mRNA. The downregulation of AT(1a)R expression under hyperosmotic conditions may be an important mechanism by which the activity of ANG II is regulated in the hyperosmotic renal medulla.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Équilibre hydroélectrolytique
/
Régulation de l'expression des gènes
/
Récepteur de type 1 à l'angiotensine-II
/
Médulla rénale
Limites:
Animals
Langue:
En
Journal:
Am J Physiol Regul Integr Comp Physiol
Sujet du journal:
FISIOLOGIA
Année:
2006
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique