Abstract: The present invention relates to novel mammalian catecholamine receptor proteins and genes that encode such proteins. The invention is directed toward the isolation and characterization of mammalian catecholamine receptor proteins. The invention specifically provides isolated complementary DNA copies of mRNA corresponding to rat and human homologues of a mammalian catecholamine receptor gene. Also provided are recombinant expression constructs capable of expressing the mammalian catecholamine receptor genes of the invention in cultures of transformed prokaryotic and eukaryotic cells, as well as such cultures of transformed cells that synthesize the mammalian catecholamine receptor proteins encoded therein. The invention also provides methods for screening compounds in vitro that are capable of binding to the mammalian catecholamine receptor proteins of the invention, and further characterizing the binding properties of such compounds in comparison with known catecholamine receptor agonists and antagonists.

Abstract: The present invention provides recombinant expression constructs comprising nucleic acid encoding mammalian melanocortin receptors, in particular MC-4 melanocortin receptor, and mammalian cells into which said recombinant expression constructs have been introduced that express functional mammalian MC-4 melanocortin receptors. The invention particularly provides such genetically engineered cells expressing the human MC4-R melanocortin receptor for screening compounds for receptor agonist and antagonist activity. The invention also provides screening methods using genetically engineered cells expressing the human MC-4 melanocortin receptor to specifically detect and identify agonists and antagonists for this melanocortin receptor. Such screening methods are provided identifying compounds with MC-4 melanocortin receptor antagonist activity having the capacity to influence or modify metabolism and feeding behavior, particularly pathological feeding behavior such as illness-induced cachexia.

Abstract: The present invention relates to the isolation, characterization and pharmacological uses for the human D5 dopamine receptor, the gene corresponding to this receptor, pseudogenes of this receptor gene, a recombinant eukaryotic expression vector capable of expressing the human D5 dopamine receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize the human D5 dopamine receptor. The invention relates to the biochemical and physiological characterization of the human D5 dopamine receptor and the development and testing of drugs useful for treating or preventing human disease.

Abstract: The present invention relates to a novel mammalian methadone-specific opioid receptor protein and genes that encode a such protein. The invention is directed toward the isolation, characterization and pharmacological use of mammalian methadone-specific opioid receptor proteins. The invention specifically provides isolated complementary DNA copies of mRNA corresponding to the rat homologue or the mammalian methadone-specific opioid receptor gene. Also provided are recombinant expression constructs capable of expressing the mammalian methadone-specific opioid receptor genes of the invention in cultures of transformed prokaryotic and eukaryotic cells, as well as such cultures of transformed cells that synthesize the mammalian methadone-specific opioid receptor proteins encoded therein.

Abstract: The present invention relates to novel mammalian amino acid transporter proteins and the genes that encode such proteins. The invention is directed toward the isolation, characterization and pharmacological use of the human amino acid transporter proteins EAAT1, EAAT2, EAAT3 and ASCT1. The invention specifically provides isolated complementary DNA copies of mRNA corresponding to each of these transporter genes. Also provided are recombinant expression constructs capable of expressing each of the amino acid transporter genes of the invention in cultures of transformed prokaryotic and eukaryotic cells, as well as such cultures of transformed cells that synthesize the human amino acid transporter proteins encoded therein. The invention also provides methods for screening in vitro compounds having transport-modulating properties using preparations of transporter proteins from such cultures of cells transformed with recombinant expression constructs.

Abstract: This invention relates to methods and reagents for inhibiting furin endoprotease activity and specifically for inhibiting furin endoprotease-mediated maturation of bioactive proteins in vivo and in vitro. The invention specifically provides proteins capable of inhibiting furin endoprotease activity. Particularly provided are .alpha..sub.1 -antitrypsin variants that specifically inhibit furin endoprotease activity. Methods for using furin endoprotease inhibition to attenuate or prevent viral protein maturation, and thereby alleviate viral infections, are provided. Also provided are methods for using furin endoprotease inhibition to attenuate or prevent proteolytic processing of bacterial toxins, thereby alleviating bacterial infections. Methods are also provided to inhibit proteolytic processing of biologically active proteins and peptides. The invention also provides pharmaceutically acceptable compositions of therapeutically effective amounts of furin endoprotease inhibitors.

Abstract: This invention herein describes a method of facilitating the entry of drugs into cells at pharmokinetically useful levels and also a method of targeting drugs to specific organelles within the cell. This lipid/drug conjugate targeting invention embodies an advance over other drug targeting methods because through this method, intracellular drug concentrations may reach levels which are orders of magnitude higher than those achieved otherwise. Furthermore, it refines the drug delivery process by allowing therapeutic agents to be directed to certain intracellular structures. This technology is appropriate for use with antiproliferative drugs, in particular in combination with a multiplicity of other emolients and agents to make up topically-active substances such as salves, for rapid and efficient introduction of antiproliferative agents through the epidermis for treatment of skin diseases such as psoriasis.

Abstract: The present invention relates to a mammalian melanocyte stimulating hormone receptor. The invention is directed toward the isolation, characterization and pharmacological use of mammalian melanocyte stimulating hormone receptor, the gene corresponding to this receptor, a recombinant eukaryotic expression construct capable of expressing a mammalian melanocyte stimulating hormone receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize mammalian melanocyte stimulating hormone receptor. The invention also provides methods for screening MSH.sup.R agonists and antagonists in vitro using preparations of receptor from such cultures of eukaryotic cells transformed with a recombinant eukaryotic expression construct comprising the MSH.sup.R receptor gene. The invention specifically provides human and mouse MSH.sup.R genes.

Abstract: The present invention is directed toward the isolation, characterization and pharmacological use of the human D4 dopamine receptor. The nucleotide sequence of the gene corresponding to this receptor and alleleic variants thereof are provided by the invention. The invention particularly provides recombinant eukaryotic expression constructs capable of expressing the human D4 dopamine receptor at useful levels in cultures of transformed eukaryotic cells. The invention provides cultures of transformed eukaryotic cells which synthesize such useful amounts of human D4 dopamine receptor protein, and methods for characterizing novel psychotropic compounds using such cultures.

Abstract: A method for treating circadian rhythm disorders is described. The method involves the administration of melatonin from about 6 hours to about 19 hours prior to when the normal sleep phase should begin, depending on whether a phase advance shift in circadian rhythms or a phase delay shift is desired. This is typically from about 4 hours to about 17 hours prior to the time of endogenous melatonin onset.