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AssigneeSynaptic Pharmaceutical Corporation
InventorsJonathan A. Bard, Richard L. Weinshank, Carlos C. Forray
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This invention provides an isolated nucleic acid, vectors, transformed mammalian cells and non-human transgenic animals that encode and express normal or mutant alpha 1a, alpha 1b and alpha 1c adrenergic receptor genes. This invention also provides a protein, and an antibody directed to the protein and pharmaceutical compounds related to alpha 1a, alpha 1b and alpha 1c adrenergic receptors. This invention provides nucleic acid probes, and antisense oligonucleotides complementary to alpha 1a, alpha 1b and alpha 1c adrenergic receptor genes. This invention further provides methods for determining ligand binding, detecting expression, drug screening, and treatments for alleviating abnormalities associated with human alpha 1a, alpha 1b and alpha 1c adrenergic receptors.
An isolated nucleic molecule encoding a human α1 adrenergic receptor.
A plasmid designated pCEXV-α1a.
A plasmid designated pcEXV-α1b.
A plasmid designated pcEXV-α1c.
A nucleic acid probe comprising a nucleic acid molecule of at least 15 nucleotides capable of specifically hybridizing with a sequence included within the sequence of a nucleic acid molecule encoding a human α1a receptor.
A nucleic acid probe comprising a nucleic acid molecule of at least 15 nucleotides capable of specifically hybridizing with a sequence included within the sequence of a nucleic acid molecule encoding a human α1b receptor.
A nucleic acid probe comprising a nucleic acid molecule of at least 15 nucleotides capable of specifically hybridizing with a sequence included within the sequence of a nucleic acid molecule encoding a human α1c receptor.
An antisense oligonucleotide having a sequence capable of specifically binding to a mRNA molecule encoding a human α1a adrenergic receptor so as to prevent translation of the mRNA molecule.
An antisense oligonucleotide having a sequence capable of specifically binding to a mRNA molecule encoding a human α1b adrenergic receptor so as to prevent translation of the mRNA molecule.
An antisense oligonucleotide having a sequence capable of specifically binding to a mRNA molecule encoding a human α1c adrenergic receptor so as to prevent translation of the mRNA molecule.
An isolated human α1 adrenergic receptor protein.
An antibody directed to a human α1a adrenergic receptor or to a protein fragment of the human α1a adrenergic receptor.
An antibody directed to a human α1b adrenergic receptor or to a protein fragment of the human α1b adrenergic receptor.
An antibody directed to a human α1c adrenergic receptor or a protein fragment of the human α1c adrenergic receptor.
A pharmaceutical composition comprising an amount of a substance effective to alleviate the abnormalities resulting from overexpression of a human α1a adrenergic receptor and a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising an amount of a substance effective to alleviate the abnormalities resulting from overexpression of a human α1b adrenergic receptor and a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising an amount of a substance effective to alleviate the bnormalities resulting from overexpression of a human α1c adrenergic receptor and a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising an amount of a substance effective to alleviate abnormalities resulting from underexpression of a human α1a adrenergic receptor and a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising an amount of a substance effective to alleviate abnormalities resulting from underexpression of a human α1b adrenergic receptor and a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising an amount of a substance effective to alleviate abnormalities resulting from underexpression of a human α1c adrenergic receptor and a pharmaceutically acceptable carrier.
A method of determining the physiological effects of varying the levels of expression of a specific human α1 adrenergic receptor which comprises producing a transgenic non-human mammal whose levels of expression of a human α1 adrenergic receptor can be varied by use of an inducible promoter.
A method of determining the physiological effects of expressing varying levels of a specific human α1 adrenergic receptor which comprises producing a panel of transgenic non-human mammals each expressing a different amount of a human α1 adrenergic receptor.
A method of determining whether a ligand not known to be capable of specifically binding to a human α1 adrenergic receptor can specifically bind to a human α1 adrenergic receptor, which comprises contacting a mammalian cell comprising a plasmid which further comprises a DNA molecule adapted for expression in a mammalian cell which allows subject cell to express a human α1 adrenergic receptor on the cell surface with the ligand under conditions permitting binding of ligands known to bind to a human α1 adrenergic receptor, detecting the presence of any ligand bound to the human α1 adrenergic receptor, the presence of bound ligand thereby determining the ligand binds to the human α1 adrenergic receptor, and thereby determining whether the ligand binds to the human α1 adrenergic receptor.
A method of screening drugs to identify drugs which interact with, and bind to, a human α1 adrenergic receptor on the surface of a cell, which comprises contacting a mammalian cell which comprises a plasmid adapted for expression in a mammalian cell which further comprises a DNA molecule which expresses a human α1 adrenergic receptor on the cell surface with a plurality of drugs, determining those drugs which bind to the human α1a adrenergic receptor expressed on the cell surface of the mammalian cell, and thereby identifying drugs which interact with, and bind to, the human α1 adrenergic receptor.
A method of determining whether a ligand not known to be capable of binding to a human α1 adrenergic receptor can bind to a human α1 adrenergic receptor, which comprises preparing a cell extract from mammalian cells, which comprise a plasmid adapted for expression in a mammal, which further comprise a DNA molecule which expresses a human α1 adrenergic receptor on the cell surface, isolating a membrane fraction from the cell extract, incubating the ligand with the membrane fraction under conditions permitting binding of ligands known to bind to the human α1 adrenergic receptor, detecting the presence of any bound ligand, and thereby determining whether the ligand binds to the human α1 adrenergic receptor.
A method of screening drugs to identify drugs that interact with, and bind to, an α1 adrenergic receptor, which comprises preparing a cell extract from mammalian cells, which comprise a plasmid adapted for expression in a mammalian cell which further comprise a DNA molecule which expresses a human α1 adrenergic receptor on the cell surface, isolating a membrane fraction from the cell extract, incubating the membrane fraction with a plurality of drugs, determining those drugs which interact with and bind to the human α1 adrenergic receptor, and thereby identifying drugs which interact with, and bind to, the human α1 adrenergic receptor.
A method of identifying a ligand which interacts with, and activates or blocks the activation of, a a human α1 adrenergic receptor on the surface of a cell, which comprises contacting a mammalian cell which comprises a plasmid adapted for expression in a mammalian cell which further comprises a DNA molecule which expresses a human α1 adrenergic receptor on the cell surface with the ligand, determining whether the ligand activates or blocks the activation of the receptor using a bioassay such as second messenger assays, and thereby identifying a ligand which interacts with, and activates or blocks the activation of, a human α1 adrenergic receptor.
A method for identifying a ligand which is capable of binding to and activating or inhibiting a human α1 adrenergic receptor, which comprises contacting a mammalian cell, wherein the membrane lipids have been labelled by prior incubation with a labelled myo-inositol phosphate molecule, the mammalian cell comprising a plasmid adapted for expression in a mammalian cell which further comprises a DNA molecule which expresses a human α1 adrenergic receptor with the ligand and identifying an inositol phosphate metabolite released from the membrane lipid as a result of ligand binding to and activating an α1 adrenergic receptor.
A method for identifying a ligand that is capable of binding to and activating or inhibiting a human α1 adrenergic receptor, wherein the binding of ligand to the adrenergic receptor results in a physiological response, which comprises contacting a mammalian cell which comprises a plasmid adapted for expression in a mammalian cell which further comprises a DNA molecule which expresses a human α1 adrenergic receptor with a calcium sensitive fluorescent indicator, removing the indicator that has not been taken up by the cell, contacting the cells with the ligand and identifying an increase or decrease in intracellular Ca+2 as a result of ligand binding to and activating the receptor.
Dependencies are inferred from the claim text.