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Relationship between internalization and mRNA decay in down-regulation of recombinant type 1 angiotensin II receptor (AT1) expression in smooth muscle cells.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Adams, Bill Obertone, Tracy Sitler Wang, Xiao-Fei Murphy, T. J. |
| Copyright Year | 1999 |
| Abstract | 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. |
| Starting Page | 994 |
| Ending Page | 1001 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.pharm.emory.edu/tmurphy/MP55_1028.pdf |
| PubMed reference number | 10347244v1 |
| Volume Number | 55 |
| Issue Number | 6 |
| Journal | Molecular pharmacology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Angiotensin I Angiotensin II Angiotensins Anhydrotetracycline Combined Modality Therapy Disease Vectors Down-Regulation Muscle Cells Muscle, Smooth, Vascular Myocytes, Smooth Muscle Recombinants Retroviridae Smooth muscle (tissue) Tetracycline Transmembrane Domain |
| Content Type | Text |
| Resource Type | Article |
