Identification of the receptor subtype responsible for endothelin-mediated protein kinase C activation and atrial natriuretic factor secretion from atrial myocytes
| Autor: | C E Irons, Christopher C. Glembotski, S F Murray |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
medicine.hormone
medicine.medical_specialty Cell Biology Biology Biochemistry Endothelins chemistry.chemical_compound Endocrinology Atrial natriuretic peptide chemistry Internal medicine cardiovascular system medicine Myocyte Secretion Phosphatidylinositol Receptor Endothelin receptor Molecular Biology Protein kinase C |
| Zdroj: | Journal of Biological Chemistry. 268:23417-23421 |
| ISSN: | 0021-9258 |
| Popis: | Endothelin-1 (ET-1) is a potent stimulator of atrial natriuretic factor (ANF) secretion from myocardial cells. In heart tissue there are two ET receptor subtypes (ETA-R and ETB-R), which can be pharmacologically distinguished by the ET isopeptides ET-1 and ET-3. However, the identification of the ET-R subtype responsible for the rapid enhancement of ANF release, which occurs within minutes of exposing cardiac myocytes to ET, has not been investigated. In the present study ET-1 was about 100-fold more potent than ET-3 at stimulating membrane phosphoinositide hydrolysis, protein kinase C activation, and ANF release from purified primary atrial myocytes. These responses were completely abolished by BQ123, an ETA-R antagonist. Radioligand binding analyses showed that competitor peptides displaced 125I-ET-1 binding to atrial myocyte ET-Rs with a rank order of potency of ET-1 >> BQ123 > ET-3, a characteristic ETA-R pharmacological profile. While neither ET-1 or ET-3 altered forskolin-stimulated cAMP levels, suggesting the absence of the ETB-R, basal cAMP levels were also unaffected by the ETs. Northern analysis using ET-R subtype-specific probes demonstrated that the ETA-R transcript was present in the cultures at levels at least 50-fold greater than the ETB-R transcript. These findings demonstrate that the stimulation of the phosphatidylinositol/protein kinase C pathway, which is required for maximal ET-stimulated ANF release from primary atrial myocytes, is associated with the activation of only the ETA-R, thus defining a specific function for an endogenous ET-R in myocardial cells. |
| Databáze: | OpenAIRE |
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