Phorbol esters promote alpha 1-adrenergic receptor phosphorylation and receptor uncoupling from inositol phospholipid metabolism.

Détails

ID Serval
serval:BIB_91F138D473B9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Phorbol esters promote alpha 1-adrenergic receptor phosphorylation and receptor uncoupling from inositol phospholipid metabolism.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Leeb-Lundberg L.M., Cotecchia S., Lomasney J.W., DeBernardis J.F., Lefkowitz R.J., Caron M.G.
ISSN
0027-8424 (Print)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
1985
Volume
82
Numéro
17
Pages
5651-5655
Langue
anglais
Résumé
DDT1 MF-2 cells, which are derived from hamster vas deferens smooth muscle, contain alpha 1-adrenergic receptors (54,800 +/- 2700 sites per cell) that are coupled to stimulation of inositol phospholipid metabolism. Incubation of these cells with tumor-promoting phorbol esters, which stimulate calcium- and phospholipid-dependent protein kinase, leads to a marked attenuation of the ability of alpha 1-receptor agonists such as norepinephrine to stimulate the turnover of inositol phospholipids. This turnover was measured by determining the 32P content of phosphatidylinositol and phosphatidic acid after prelabeling of the cellular ATP pool with 32Pi. These phorbol ester-treated cells also displayed a decrease in binding affinity of cellular alpha 1 receptors for agonists with no change in antagonist affinity. By using affinity chromatography on the affinity resin Affi-Gel-A55414, the alpha 1 receptors were purified approximately equal to 300-fold from control and phorbol ester-treated 32Pi-prelabeled cells. As assessed by NaDodSO4/polyacrylamide gel electrophoresis, the Mr 80,000 alpha 1-receptor ligand-binding subunit is a phosphopeptide containing 1.2 mol of phosphate per mol of alpha 1 receptor. After phorbol ester treatment this increased to 3.6 mol of phosphate per mol of alpha 1 receptor. The effect of phorbol esters on norepinephrine-stimulated inositol phospholipid turnover and alpha 1-receptor phosphorylation showed the same rapid time course with a t1/2 less than 2 min. These results indicate that calcium- and phospholipid-dependent protein kinase may play an important role in regulating the function of receptors that are coupled to the inositol phospholipid cycle by phosphorylating and deactivating them.
Mots-clé
Animals, Cell Line, Cricetinae, Enzyme Activation/drug effects, Male, Molecular Weight, Norepinephrine/pharmacology, Phorbols/pharmacology, Phosphatidylinositols/metabolism, Phosphoproteins/metabolism, Phosphorylation, Protein Kinase C, Protein Kinases/metabolism, Receptors, Adrenergic, alpha/metabolism, Tetradecanoylphorbol Acetate/pharmacology, Vas Deferens
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 14:55
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