Abstract: Metabotropic receptor mGluR7 is identified and sequenced. The mGluR7 receptor subfamily mediates inhibition of transmitter release at selected glutamatergic synapses. The receptors, mGluR7-specific peptides and antibodies thereto are used to identify agonists and antagonists of G protein coupled glutamate receptor mediated neuronal transmitter release, as well as in methods of diagnosis and therapy.

Abstract: Metabotropic receptor mGluR7 is identified and sequenced. The mGluR7 receptor subfamily mediates inhibition of transmitter release at selected glutamatergic synapses. The receptors, mGluR7-specific peptides and antibodies thereto are used to identify agonists and antagonists of G protein coupled glutamate receptor mediated neuronal transmitter release, as well as in methods of diagnosis and therapy.

Abstract: The present invention provides compositions and methods useful for isolating calcineurin as well as inhibiting calcineurin activity. The compositions are peptides that contain regions that are homologous to calcineurin-binding regions of AKAP 79. Also provided are methods for determining if a cell contains a calcineurin-binding and PKA-binding anchoring protein that are useful for identifying additional proteins that bind both calcineurin and PKA.

Abstract: The present invention provides compositions and methods useful for isolating calcineurin as well as inhibiting calcineurin activity. The compositions are peptides that contain regions that are homologous to calcineurin-binding regions of AKAP 79. Also provided are methods for determining if a cell contains a calcineurin-binding and PKA-binding anchoring protein that are useful for identifying additional proteins that bind both calcineurin and PKA. Another aspect of the present invention is methods for enhancing expression of interleukin 2 by T cells.

Abstract: Metabotropic receptor mGluR7 is identified and sequenced. The mGluR7 receptor subfamily mediates inhibition of transmitter release at selected glutamatergic synapses. The receptors, mGluR7-specific peptides and antibodies thereto are used to identify agonists and antagonists of G protein coupled glutamate receptor mediated neuronal transmitter release, as well as in methods of diagnosis and therapy.

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: The present invention provides compositions and methods useful for isolating calcineurin as well as inhibiting calcineurin activity. The compositions are peptides that contain regions that are homologous to calcineurin-binding regions of AKAP 79. Also provided are methods for determining if a cell contains a calcineurin-binding and PKA-binding anchoring protein that are useful for identifying additional proteins that bind both calcineurin and PKA.

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: The present invention is directed toward the isolation, characterization and pharmacological use of the human D.sub.4 dopamine receptor. The nucleotide sequence of the gene corresponding to this receptor is provided by the invention. The invention also includes a recombinant eukaryotic expression vector capable of expressing the human D.sub.4 dopamine receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells which synthesize the human D.sub.4 dopamine receptor.

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 variant thereof are provided by the invention. The invention also includes recombinant eukaryotic expression constructs capable of expressing the human D4 dopamine receptor in cultures of transformed eukaryotic cells. The invention provides cultures of transformed eukaryotic cells which synthesize the human D4 dopamine receptor, and methods for characterizing novel psychotropic compounds using such cultures.

Abstract: The present invention relates to a mammalian adrenocorticotropic hormone receptor. The invention is directed toward the isolation, characterization and pharmacological use of mammalian adrenocorticotropic hormone receptor, the gene corresponding to this receptor, a recombinant eukaryotic expression construct capable of expressing a mammalian adrenocorticotropic hormone receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize mammalian adrenocorticotropic hormone receptor. The invention also provides methods for screening ACTH.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 ACTH.sup.R receptor gene. The invention specifically provides human and bovine ACTH.sup.R genes.

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: Novel, modified Taq DNA polymerases and genes encoding for them are disclosed. The modified Taq DNA polymerases of the invention are the same size, have the same heat stability and synthesis rate as the native enzyme, but lack the 5'-3' exonuclease activity. As a result of this modification, the enzymes have improved processivity as compared to the native enzyme.The enzymes of the present invention enable improved methods of conducting PCR, DNA sequencing, and DNA synthesis.

Abstract: The present invention relates to a novel mammalian adenosine receptor. The invention is directed toward the isolation, characterization and pharmacological use of the rat A3 adenosine receptor, the gene corresponding to this receptor, a recombinant eukaryotic expression construct capable of expressing the rat A3 adenosine receptor in cultures of transformed eukaryotic cells and such cultures of transformed eukaryotic cells that synthesize the rat A3 adenosine receptor. The invention also provides methods for screening adenosine-receptor agonists and antagonists in vitro using preparations of the rat A3 adenosine receptor from such cultures of eukaryotic cells transformed with a recombinant eukaryotic expression construct comprising the rat A3 adenosine receptor gene.

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: 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.