Glucose-induced downregulation of angiotensin II and arginine vasopressin receptors in cultured rat aortic vascular smooth muscle cells. Role of protein kinase C
| Autor: | R W Schrier, B Williams, Phoebe Tsai |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Receptors
Vasopressin Vasopressin medicine.medical_specialty Vascular smooth muscle Down-Regulation Muscle Smooth Vascular Downregulation and upregulation Internal medicine medicine Animals Receptor Aorta Cells Cultured Protein Kinase C Protein kinase C Vasopressin receptor Receptors Angiotensin Dose-Response Relationship Drug business.industry Angiotensin II General Medicine Rats Arginine Vasopressin Enzyme Activation Glucose Endocrinology Hormone receptor cardiovascular system Calcium business hormones hormone substitutes and hormone antagonists Research Article |
| Zdroj: | Journal of Clinical Investigation. 90:1992-1999 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci116079 |
| Popis: | Early diabetes mellitus is characterized by impaired responses to pressor hormones and pressor receptor downregulation. The present study examined the effect of elevated extracellular glucose concentrations on angiotensin II (AII) and arginine vasopressin (AVP) receptor kinetics in cultured rat vascular smooth muscle cells (VSMC). Scatchard analysis of [3H]AVP and 125I-AII binding to confluent VSMC showed that high glucose concentrations (20 mM) similarly depressed AVP and AII surface receptor Bmax but did not influence receptor Kd. This receptor downregulation was not reproduced by osmotic control media containing either L-glucose or mannitol. Receptor downregulation was maximal at a glucose concentration of 15-20 mM and required 24-48 h for a maximum effect. Normalization of the extracellular glucose concentration allowed complete recovery of AVP and AII binding within 48 h. Receptor downregulation was associated with depressed AVP and AII-stimulated intracellular signaling and cell contraction. High glucose concentrations induced a sustained activation of protein kinase C (PKC) in VSMC, which was prevented by coincubation with H-7. H-7 also markedly attenuated glucose-induced downregulation of AVP and AII receptors on VSMC. This study demonstrates a novel cellular mechanism whereby high extracellular glucose concentrations directly and independently downregulate pressor hormone receptors and their function on vascular tissue via glucose-stimulated PKC activation. |
| Databáze: | OpenAIRE |
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