RT Journal Article SR Electronic T1 Relationship between Internalization and mRNA Decay in Down-Regulation of Recombinant Type 1 Angiotensin II Receptor (AT1) Expression in Smooth Muscle Cells JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1028 OP 1036 DO 10.1124/mol.55.6.1028 VO 55 IS 6 A1 Brian Adams A1 Tracy S. Obertone A1 Xiaofei Wang A1 T. J. Murphy YR 1999 UL http://molpharm.aspetjournals.org/content/55/6/1028.abstract AB 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.