Constitutive activity and inverse agonism at the alpha1adrenoceptors.

Details

Serval ID
serval:BIB_A3A81F7D34BE
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Constitutive activity and inverse agonism at the alpha1adrenoceptors.
Journal
Biochemical Pharmacology
Author(s)
Cotecchia S.
ISSN
0006-2952 (Print)
ISSN-L
0006-2952
Publication state
Published
Issued date
2007
Volume
73
Number
8
Pages
1076-1083
Language
english
Abstract
Mutations of G protein-coupled receptors (GPCR) can increase their constitutive (agonist-independent) activity. Some of these mutations have been artificially introduced by site-directed mutagenesis, others occur spontaneously in human diseases. The alpha(1B)adrenoceptor was the first GPCR in which point mutations were shown to trigger receptor activation. This article briefly summarizes some of the findings reported in the last several years on constitutive activity of the alpha(1)adrenoceptor subtypes, the location where mutations have been found in the receptors, the spontaneous activity of native receptors in recombinant as well as physiological systems. In addition, it will highlight how the analysis of the pharmacological and molecular properties of the constitutively active adrenoceptor mutants provided an important contribution to our understanding of the molecular mechanisms underlying the mechanism of receptor activation and inverse agonism.
Keywords
Adrenergic alpha-1 Receptor Antagonists, Adrenergic alpha-Antagonists/pharmacology, Amino Acid Sequence, Animals, COS Cells, Cercopithecus aethiops, Cricetinae, GTP-Binding Proteins/metabolism, Humans, Models, Molecular, Molecular Sequence Data, Mutation, Protein Conformation, Protein Structure, Secondary, Receptors, Adrenergic, alpha-1/chemistry, Receptors, Adrenergic, alpha-1/genetics, Receptors, G-Protein-Coupled/metabolism
Pubmed
Web of science
Create date
24/01/2008 11:05
Last modification date
20/08/2019 15:09
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