Abstract: The present invention provides a &bgr;arrestin knockout mouse useful for screening compounds for efficacy in controlling pain, methods of controlling pain in subjects by inhibiting binding of &bgr;arrestin to phosphorylated &mgr; opioid receptors, and methods of screening a compound for activity in potentiating &mgr; opioid receptor agonist activity (e.g., morphine activity) by determining whether or not said compound inhibits &bgr;arrestin binding to a phosphorylated &mgr; opioid receptor.

Abstract: Desensitization of receptors that control disease is prevented by inhibiting G-protein receptor kinases. This has applicability, e.g., for patients with heart failure or on a left ventricular heart device or a heart pump after surgery or about to undergo surgery and at high risk for a cardiac event of on an opiate or addicted to opiate or with cystic fibrosis or rheumatoid arthritis.

Abstract: The present invention provides a &bgr;arrestin knockout mouse useful for screeening compounds for efficacy in controlling pain, methods of controlling pain in subjects by inhibiting binding of &bgr;arrestin to phosphorylated &mgr; opioid receptors, and methods of screening a compound for activity in potentiating &mgr; opioid receptor agonist activity (e.g., morphine activity) by determining whether or not said compound inhibits &bgr;arrestin binding to a phosphorylated &mgr; opioid receptor.

Abstract: The present invention deals with gene therapy for treating chronic heart failure and other cardiac disease states which are accompanied by a reduced number or functioning of myocardial beta-adrenergic receptors (&bgr;-AR). &bgr;-AR receptor function is augmented in transgenic animals by delivery and expression of a beta-2-adrenergic receptor gene or a gene encoding a beta adrenergic receptor kinase inhibitor, resulting in increased in vivo left ventricular function. The present invention includes recombinant plasmid vectors, alternative beta-adrenergic receptor gene delivery strategies, and transgenic mice carrying a &bgr;-AR transgene, a &bgr;-ARK transgene, or a &bgr;-ARK inhibitor transgene.

Abstract: The present invention relates, in general, to myocardial hypertrophy and, in particular, to agents that inhibit cardiac Gq-coupled receptor signaling and to methods of inhibiting myocardial hypertrophy using same.

Abstract: The present invention deals with gene therapy for treating chronic heart failure and other cardiac disease states which are accompanied by a reduced number or functioning of myocardial beta-adrenergic receptors (&bgr;-AR). &bgr;-AR receptor function is augmented in transgenic animals by delivery and expression of a beta-2-adrenergic receptor gene or a gene encoding a beta adrenergic receptor kinase inhibitor, resulting in increased in vivo left ventricular function. The present invention includes recombinant plasmid vectors, alternative beta-adrenergic receptor gene delivery strategies, and transgenic mice carrying a &bgr;-AR transgene, a &bgr;-ARK transgene, or a &bgr;-ARK inhibitor transgene.

Abstract: The present invention relates, in general, to myocardial hypertrophy and, in particular, to agents that inhibit cardiac Gq-coupled receptor signaling and to methods of inhibiting myocardial hypertrophy using same.

Abstract: Disclosed is a transformed yeast cell containing a first heterologous DNA sequence which codes for a mammalian G protean coupled receptor and a second heterologous DNA sequence which codes for a mammalian G protein &agr; subunit (mammalian G&agr;). The first and second heterologous DNA sequences are capable of expression in the cell, but the cell is incapable of expressing an endogenous G protein &agr;-subunit (yeast G&agr;). The cells are useful for screening compounds which affect the rate of dissociation of G&agr; from G&bgr;&tgr; in a cell.

Abstract: Disclosed is a transformed yeast cell containing a first heterologous DNA sequence which codes for a mammalian G protein coupled receptor and a second heterologous DNA sequence which codes for a mammalian G protein &agr; subunit (mammalian G&agr;). The first and second heterologous DNA sequences are capable of expression in the cell, but the cell is incapable of expressing an endogenous G protein &agr;-subunit (yeast G&agr;) The cells are useful for screening compounds which affect the rate of dissociation of G&agr; from G&bgr;&ggr; in a cell. Also disclosed is a novel DNA expression vector useful for making cells as described above. The vector contains a first segment comprising at least a fragment of the extreme amino-terminal coding sequence of a yeast G protein coupled receptor. A second segment is positioned downstream from the first segment (and in correct reading frame therewith), with the second segment comprising a DNA sequence encoding a heterologous G protein coupled receptor.

Abstract: The present invention relates to a method of inhibiting desensitization of a cell to the effects of a compound. The method comprises contacting the cell with an agent capable of inhibiting phosphorylation, by a protein kinase, of a receptor for the compound present on the surface of the cell. The present invention also relates to a method of screening a compound for its ability to inhibit desensitization. The method comprises: i) contacting a receptor specific kinase-containing sample with the compound under conditions such that interaction between receptor specific kinase present in the sample and the compound can occur, andii) determining the ability of the receptor specific kinase to phosphorylate the receptor for which it is specific.

Abstract: The present invention relates, in general, to vascular smooth muscle proliferation and, in particular, to a method of inhibiting arterial and venous smooth muscle proliferation resulting, for example, from arterial injury or vein grafting. The invention also relates to an expression construct encoding a G.beta..gamma. inhibitor suitable for use in such a method.

Abstract: Disclosed is a transformed yeast cell containing a first heterologous DNA sequence which codes for a mammalian G protein coupled receptor and a second heterologous DNA sequence which codes for a mammalian G protein .alpha. subunit (mammalian G.sub..alpha.). The first and second heterologous DNA sequences are capable of expression in the cell, but the cell is incapable of expressing an endogenous G protein .alpha.-subunit (yeast G.sub..alpha.). The cells are useful for screening compounds which affect the rate of dissociation of G.sub..alpha. from G.sub..beta..tau. in a cell. Also disclosed is a novel DNA expression vector useful for making cells as described above. The vector contains a first segment comprising at least a fragment of the extreme amino-terminal coding sequence of a yeast G protein coupled receptor.

Abstract: A recombinant cell comprising a host cell containing a recombinant DNA sequence is disclosed. The recombinant DNA sequence comprises vector DNA and DNA which encodes a mammalian adrenergic receptor. The host cell is one capable of undergoing proliferation in response to activation of the adrenergic receptor. In one specific embodiment of the foregoing, the adrenergic receptor includes a mutation in the third cytoplasmic loop thereof which renders the adrenergic receptor constitutively active, and the host cell undergoes proliferation in response to the constitutively active adrenergic receptor. Also disclosed are in vitro assays employing the foregoing which are useful for screening test compounds for antitumor and antiatherogenic activity, along with a diagnostic assay for detecting the oncogenic activation of cells in a patient.

Abstract: Disclosed is a transformed yeast cell containing a first heterologous DNA sequence which codes for a mammalian G protein coupled receptor and a second heterologous DNA sequence which codes for a mammalian G protein .alpha. subunit (mammalian G.sub..alpha.). The first and second heterologous DNA sequences are capable of expression in the cell, but the cell is incapable of expressing an endogenous G protein .alpha.-subunit (yeast G.sub..alpha.). The cells are useful for screening compounds which affect the rate of dissociation of G.sub..alpha. from G.sub..beta..gamma. in a cell. Also disclosed is a novel DNA expression vector useful for making cells as described above. The vector contains a first segment comprising at least a fragment of the extreme amino-terminal coding sequence of a yeast G protein coupled receptor.