Multiple second messenger pathways of alpha-adrenergic receptor subtypes expressed in eukaryotic cells.

Détails

ID Serval
serval:BIB_3C0AF19FFFA0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Multiple second messenger pathways of alpha-adrenergic receptor subtypes expressed in eukaryotic cells.
Périodique
Journal of Biological Chemistry
Auteur(s)
Cotecchia S., Kobilka B.K., Daniel K.W., Nolan R.D., Lapetina E.Y., Caron M.G., Lefkowitz R.J., Regan J.W.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
1990
Peer-reviewed
Oui
Volume
265
Numéro
1
Pages
63-69
Langue
anglais
Résumé
The alpha-adrenergic receptors mediate the effects of epinephrine and norepinephrine on cellular signaling systems via guanine nucleotide binding regulatory proteins (G-proteins). Three alpha-adrenergic receptor subtypes have been cloned: the alpha 1, the alpha 2-C10, and the alpha 2-C4 adrenergic receptors. To investigate functional differences between the different subtypes, we assessed the ability of each to interact with adenylyl cyclase and polyphosphoinositide metabolism by permanently and transiently expressing the DNAs encoding the alpha 1, the alpha 2-C10, and the alpha 2-C4 adrenergic receptors in cells lacking endogenous alpha-adrenergic receptors. Both alpha 2-C10 and alpha 2-C4 couple primarily to inhibition of adenylyl cyclase and to a lesser extent to stimulation of polyphosphoinositide hydrolysis. alpha 2-C10 inhibits adenylyl cyclase more efficiently than alpha 2-C4. Effects of the alpha 2-adrenergic receptors on adenylyl cyclase inhibition and on polyphosphoinositide hydrolysis are both mediated by pertussis toxin-sensitive G-proteins. The major coupling system of the alpha 1-adrenergic receptor is activation of phospholipase C via a pertussis toxin-insensitive G-protein. alpha 1-Adrenergic receptor stimulation can also increase intracellular cAMP by a mechanism that does not involve direct activation of adenylyl cyclase. As with the muscarinic cholinergic receptor family our results show that each of the alpha-adrenergic receptor subtypes can couple to multiple signal transduction pathways and suggest several generalities about the effector coupling mechanisms of G-protein-coupled receptors.
Mots-clé
Adenylate Cyclase/metabolism, Adenylate Cyclase Toxin, Animals, Cell Line, Cell Physiological Phenomena, Cricetinae, DNA/genetics, Enzyme Activation, Eukaryotic Cells/physiology, Fibroblasts, GTP-Binding Proteins/physiology, Gene Expression, Hydrolysis, Pertussis Toxin, Phosphatidylinositols/metabolism, Receptors, Adrenergic, alpha/genetics, Receptors, Adrenergic, alpha/physiology, Second Messenger Systems/physiology, Signal Transduction/physiology, Transfection, Type C Phospholipases/metabolism, Virulence Factors, Bordetella/pharmacology
Pubmed
Web of science
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 13:32
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