TY - JOUR T1 - Relationship between Internalization and mRNA Decay in Down-Regulation of Recombinant Type 1 Angiotensin II Receptor (AT<sub>1</sub>) Expression in Smooth Muscle Cells JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1028 LP - 1036 DO - 10.1124/mol.55.6.1028 VL - 55 IS - 6 AU - Brian Adams AU - Tracy S. Obertone AU - Xiaofei Wang AU - T. J. Murphy Y1 - 1999/06/01 UR - http://molpharm.aspetjournals.org/content/55/6/1028.abstract N2 - In vascular smooth muscle cells, the hormone angiotensin II is thought to cause internalization of the seven-transmembrane domain type 1 angiotensin II receptor (AT1-R) but it also suppresses expression of the receptor mRNA. As for similarly regulated members of this gene superfamily, the relative roles of these processes in receptor down-regulation are not well understood. In this study a recombinant AT1-R mRNA was synthesized in A7r5 vascular smooth muscle cells from a tetracycline-suppressible promoter using a retroviral vector system. Angiotensin II induces a profound internalization of the cell surface AT1-R protein but has no effect on steady-state AT1-R mRNA levels. Shortly after either bolus or prolonged dosing with angiotensin II, cell surface AT1-R expression recovers, indicating the existence of a significant restorative externalization pathway. The extent of this recovery is attenuated markedly when transcription of the recombinant AT1-R gene is suppressed by cotreatment of the cells with anhydrotetracycline. Although agonist-stimulated internalization appears to contribute directly to a loss of AT1-R protein, these observations provide direct evidence that a reduction in AT1-R mRNA content plays a significant role in sustained AT1-R down-regulation. ER -