Titre
Multiple second messenger pathways of alpha-adrenergic receptor subtypes expressed in eukaryotic cells.
Type
article
Institution
Externe
Périodique
Auteur(s)
Cotecchia, S.
Auteure/Auteur
Kobilka, B.K.
Auteure/Auteur
Daniel, K.W.
Auteure/Auteur
Nolan, R.D.
Auteure/Auteur
Lapetina, E.Y.
Auteure/Auteur
Caron, M.G.
Auteure/Auteur
Lefkowitz, R.J.
Auteure/Auteur
Regan, J.W.
Auteure/Auteur
Liens vers les personnes
ISSN
0021-9258
Statut éditorial
Publié
Date de publication
1990
Volume
265
Numéro
1
Première page
63
Dernière page/numéro d’article
69
Peer-reviewed
Oui
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.
Sujets
PID Serval
serval:BIB_3C0AF19FFFA0
PMID
Date de création
2008-01-24T10:05:37.944Z
Date de création dans IRIS
2025-05-20T15:54:52Z