Regulation of Angiotensin II Type 2 Receptor Gene by the Protein Kinase C–Calcium Pathway
| Autor: | Yasukiyo Mori, Naohiko Ohkubo, Hiroaki Matsubara, Katsuya Maruyama, Kazuhisa Kijima, Mitsuo Inada, Satoshi Murasawa |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_specialty
Receptors Angiotensin Myocardium Receptor expression Down-Regulation Cycloheximide Biology PC12 Cells Tropomyosin receptor kinase C Angiotensin II Rats chemistry.chemical_compound Endocrinology chemistry Internal medicine Internal Medicine medicine Animals Calcium Signal transduction Protein kinase A Receptor Protein Kinase C Protein kinase C Signal Transduction |
| Zdroj: | Hypertension. 27:529-534 |
| ISSN: | 1524-4563 0194-911X |
| Popis: | Abstract In the present study, rat angiotensin II type 2 (AT 2 ) receptor expression was upregulated in confluence-arrested PC12 cells compared with expression in proliferating cells. Treatment with cycloheximide inhibited the increase in mRNA levels in confluent cells. The state of growth arrest by serum deprivation was associated with increased expression of the AT 2 receptor, which was markedly suppressed by exposure to the active phorbol ester 12- O -tetradecanoylphorbol 13-acetate and the calcium ionophore A23187. Similar inhibitions were also observed in myocytes isolated from neonatal rat heart. The change in AT 2 mRNA levels by serum deprivation was due to the increase in the gene transcription rate. The effect of 12- O -tetradecanoylphorbol 13-acetate was mediated through decreases in gene transcription and mRNA stability, whereas A23187 affected mRNA stability. Vasoactive substances with the protein kinase C–calcium pathway, such as norepinephrine and angiotensin II, also downregulated the AT 2 mRNA level in myocytes. These findings indicate that the expression of AT 2 receptor in PC12 cells is regulated in a growth state–dependent manner, which is involved in confluence-induced new protein synthesis, thus providing a means by which cells can modulate their responsiveness to external angiotensin II stimulus. The activation of protein kinase C or calcium mobilization modifies this regulatory mechanism, suggesting that neurotransmitters or vasoactive substances with the protein kinase C–calcium pathway at least in part affect neuronal activity or blood pressure control by downregulating AT 2 receptor expression. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|