The alpha 1C-adrenergic receptor: characterization of signal transduction pathways and mammalian tissue heterogeneity.

Details

Serval ID
serval:BIB_751715ECB99D
Type
Article: article from journal or magazin.
Collection
Publications
Title
The alpha 1C-adrenergic receptor: characterization of signal transduction pathways and mammalian tissue heterogeneity.
Journal
Molecular Pharmacology
Author(s)
Schwinn D.A., Page S.O., Middleton J.P., Lorenz W., Liggett S.B., Yamamoto K., Lapetina E.G., Caron M.G., Lefkowitz R.J., Cotecchia S.
ISSN
0026-895X (Print)
ISSN-L
0026-895X
Publication state
Published
Issued date
1991
Volume
40
Number
5
Pages
619-626
Language
english
Abstract
We recently reported the cloning of a novel alpha 1-adrenergic receptor (AR), the alpha 1CAR. By transient and stable expression of the alpha 1CAR and the previously cloned alpha 1BAR in COS-7 and HeLa cells, respectively, we have now compared their ability to interact with major signal-transduction pathways (including polyphosphoinositide hydrolysis, intracellular calcium, and cAMP metabolism), as well as their mammalian tissue localization. Both alpha 1C- and alpha 1BARs primarily couple to phospholipase C via a pertussis toxin-insensitive GTP-binding protein, leading to the release of calcium from intracellular stores. Even though alpha 1C- and alpha 1BARs activate polyphosphoinositide hydrolysis by similar biochemical mechanisms, the alpha 1CAR couples to phospholipase C more efficiently than does the alpha 1BAR; activation of the alpha 1CAR results in a 2-3-fold greater increase in inositol phosphates, compared with the alpha 1BAR. Both alpha 1AR subtypes can also increase intracellular cAMP, by a mechanism that does not involve direct activation of adenylyl cyclase. In agreement with ligand binding data, the agonist methoxamine and the antagonist WB4101 are 10-fold more potent in activating or inhibiting, respectively, the ability of the alpha 1CAR to stimulate phospholipase C, compared with the alpha 1BAR. In addition, methoxamine is almost a full agonist at the alpha 1CAR, whereas it can only weakly activate the alpha 1BAR. Tissue localization, using Northern blot analysis of total and poly(A)+-selected RNA from rabbit tissues, revealed striking mammalian species heterogeneity. As previously described, the alpha 1BAR is present in several rat tissues, including heart, liver, brain, kidney, lung, and spleen, whereas the alpha 1CAR is not present in any rat tissue studied. The alpha 1BAR is also present in rabbit aorta, heart, spleen, and kidney (and absent in rabbit liver), whereas the alpha 1CAR is present in rabbit liver. Our results indicate that the cloning and expression of different alpha 1AR subtypes represents a valuable tool to elucidate functional correlates of alpha 1AR heterogeneity.
Keywords
Animals, Calcium/analysis, Calcium/pharmacology, Cyclic AMP/metabolism, Enzyme Activation, GTP-Binding Proteins/physiology, Humans, Norepinephrine/pharmacology, Phosphatidylinositols/metabolism, Rabbits, Rats, Receptors, Adrenergic, alpha/analysis, Receptors, Adrenergic, alpha/physiology, Signal Transduction, Stereoisomerism, Type C Phospholipases/analysis
Pubmed
Web of science
Create date
24/01/2008 12:05
Last modification date
20/08/2019 15:32
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