Alpha1-adrenoceptors are G-protein-coupled receptors that bind catecholamines. Sixteen distinct human alpha1A-adrenoceptor isoforms have been identified from human tissues, including five full-length and 11 truncated versions. An updated scheme for the identification of alpha1A-adrenoceptor splice variants is proposed. Given the established roles of alpha1-adrenoceptors in benign prostatic hyperplasia, myocardial hypertrophy and other cardiovascular disorders, elucidation of the biological significance of the signaling diversity and potential pharmacological roles of alpha1A-adrenoceptor splice variants are important areas of future research.
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Update on human alpha1-adrenoceptor subtype signaling and genomic organization.
Trends Pharmacol Sci
September 2004
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
Alpha1-adrenoceptors are G-protein-coupled receptors that bind catecholamines. Sixteen distinct human alpha1A-adrenoceptor isoforms have been identified from human tissues, including five full-length and 11 truncated versions. An updated scheme for the identification of alpha1A-adrenoceptor splice variants is proposed.
View Article and Find Full Text PDFHigh-affinity interactions between human alpha1A-adrenoceptor C-terminal splice variants produce homo- and heterodimers but do not generate the alpha1L-adrenoceptor.
Mol Pharmacol
August 2004
Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland, United Kingdom.
Using combinations of bioluminescence resonance energy transfer, time-resolved fluorescence resonance energy transfer and the functional complementation of pairs of inactive receptor-G protein fusion proteins, the human alpha(1A-1)-adrenoceptor was shown to form homodimeric/oligomeric complexes when expressed in human embryonic kidney (HEK) 293 cells. Saturation bioluminescence resonance energy transfer studies indicated the alpha(1A-1)-adrenoceptor homodimer interactions to be high affinity and some 75 times greater than interactions between the alpha(1A-1)-adrenoceptor and the delta opioid peptide receptor. Only a fraction of the alpha(1A-1)-adrenoceptors was at the plasma membrane of HEK293 cells at steady state.
View Article and Find Full Text PDFAlpha1-adrenoceptor subtypes.
Eur J Pharmacol
June 1999
Department of Pharmacology, Emory University Medical School, Atlanta, GA 30322, USA.
Alpha1-adrenoceptors are one of three subfamilies of receptors (alpha1, alpha2, beta) mediating responses to adrenaline and noradrenaline. Three alpha1-adrenoceptor subtypes are known (alpha1A, alpha1B, alpha1D) which are all members of the G protein coupled receptor family, and splice variants have been reported in the C-terminus of the alpha1A. They are expressed in many tissues, particularly smooth muscle where they mediate contraction.
View Article and Find Full Text PDFHuman cloned alpha1A-adrenoceptor isoforms display alpha1L-adrenoceptor pharmacology in functional studies.
Eur J Pharmacol
April 1999
Center for Biological Research, Urogenital Pharmacology, Roche Bioscience, Palo Alto, CA 94304, USA.
The recombinant alpha1A-adrenoceptor displays a distinct pharmacological profile ('classical alpha1A-adrenoceptor') in homogenate binding assays, but displays the properties of the so-called alpha1L-adrenoceptor in functional studies in whole cells at 37 degrees C. As three splice variants of the human alpha1A-adrenoceptor have been described previously (alpha1A-1, alpha1A-2 and alpha1A-3), we have compared their functional pharmacological profiles, when expressed stably in Chinese hamster ovary (CHO-K1) cells (antagonist inhibition of noradrenaline-stimulated [3H]inositol phosphates accumulation). A fourth, novel isoform (alpha1A-4) has also been studied: alpha1A-4 mRNA predominates in several human tissues including prostate, liver, heart and bladder.
View Article and Find Full Text PDFMolecular cloning, genomic characterization and expression of novel human alpha1A-adrenoceptor isoforms.
FEBS Lett
January 1998
Center for Biological Research, Neurobiology Unit, Roche Bioscience, Palo Alto, CA 94304, USA.
We have isolated and characterized from human prostate novel splice variants of the human alpha1A-adrenoceptor, several of which generate truncated products and one isoform, alpha(1A-4), which has the identical splice site as the three previously described isoforms. Long-PCR on human genomic DNA showed that the alpha(1A-4) exon is located between those encoding the alpha(1A-1) and alpha(1A-3) variants. CHO-K1 cells stably expressing alpha(1A-4) showed ligand binding properties similar to those of the other functional isoforms as well as agonist-stimulated inositol phosphate accumulation.
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