ABSTRACT
We have cloned and mapped the chromosomal location of three novel human genes encoding G protein-coupled receptors that we have named GPR6, GPR5, and GPR4. The entire coding region for each of these genes was contained on single exons. Gene GPR6 encoded a receptor that shared closest identity (71% in the transmembrane regions) with the human orphan receptor GPR3 and was localized to chromosome 6 (q21-q22.1). Northern blot analysis revealed that GPR6 transcripts were abundant in the human putamen and to a lesser extent in the frontal cortex, hippocampus, and hypothalamus. Gene GPR5 encoded a receptor that most closely resembled the orphan receptor RBS11 (48% in the transmembrane regions) and the MIP 1 alpha/RANTES receptor (45% in the transmembrane regions) and was localized to chromosome 3 (p21.3-p21.1). Gene GPR4 shared identity (40% in the transmembrane regions) with the human platelet-activating factor receptor and was localized to chromosome 19 (q13.2-q13.3).
Subject(s)
Genes/genetics , Membrane Proteins , Receptors, Cell Surface/genetics , Receptors, G-Protein-Coupled , Amino Acid Sequence , Animals , Base Sequence , Brain Chemistry , Chromosome Mapping , Cloning, Molecular , Exons/genetics , Humans , Molecular Sequence Data , Polymerase Chain Reaction , RNA, Messenger/analysis , Rats , Receptors, Cell Surface/chemistry , Receptors, Opioid/genetics , Receptors, Somatostatin/genetics , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino AcidABSTRACT
We report the isolation and characterization of several novel human genes encoding G protein-coupled receptors. Each of the receptors contained the familiar seven transmembrane topography and most closely resembled peptide binding receptors. Gene GPR1 encoded a receptor protein that is intronless in the coding region and that shared identity (43% in the transmembrane regions) with the opioid receptors. Northern blot analysis revealed that GPR1 transcripts were expressed in the human hippocampus, and the gene was localized to chromosome 15q21.6. Gene GPR2 encoded a protein that most closely resembled an interleukin-8 receptor (51% in the transmembrane regions), and this gene, not expressed in the six brain regions examined, was localized to chromosome 17q21.1-q21.3. A third gene, GPR3, showed identity (56% in the transmembrane regions) with a previously characterized cDNA clone from rat and was localized to chromosome 1p35-p36.1.
Subject(s)
Brain/metabolism , Chromosomes, Human, Pair 15 , Chromosomes, Human, Pair 17 , Chromosomes, Human, Pair 1 , GTP-Binding Proteins/genetics , Hippocampus/metabolism , Hominidae/genetics , Receptors, Cell Surface/genetics , Amino Acid Sequence , Animals , Base Sequence , Blotting, Northern , Cell Line , Chlorocebus aethiops , Chromosome Mapping , Cloning, Molecular , DNA Primers , Gene Expression , Humans , In Situ Hybridization, Fluorescence , Introns , Lymphocytes/metabolism , Molecular Sequence Data , Polymerase Chain Reaction , Rats , Receptors, Interleukin/genetics , Receptors, Interleukin-8A , Sequence Homology, Amino Acid , Transcription, Genetic , TransfectionABSTRACT
The quick, convenient, unobtrusive administration of a low dose of a drug that effectively reduces alcohol intake could be a useful adjunct to any program that aims to treat alcohol abuse. This study evaluates the ability of isoproterenol, a drug that has previously been shown to reduce ethanol intake, to exercise this action when administered as a metered aerosol mist. Rats were trained to self-administer ethanol using a procedure that limits access to a brief daily availability period. Once intake stabilized, animals were given isoproterenol by metered aerosol inhalation just before ethanol availability. A custom-designed helmet attached to a commercially available mistometer was used to deliver the drug. Isoproterenol produced a dose-dependent reduction in ethanol intake and an increase in water intake replicating the effects of parenterally administered isoproterenol on ethanol and water consumption. These findings demonstrate that the administration of isoproterenol in inhaled aerosol form can effectively reduce voluntary ethanol consumption in rats. The administration of pharmacologically active antialcohol agents via the inhalation route may be useful in the symptomatic treatment of alcohol abuse in humans.
