The United States of America As Represented by the Department of Health

Other

Johns Hopkins University

George R Uhl

Joseph P Steiner

Solomon H Snyder

Ted M Dawson

Michael J Kuhar

Valina L Dawson

Shoichi Shimada

Shigeo Kitayama

Amrat Patel

Chien-Liang Lin

Jai-Bel Wang

David Vandenbergh

C Mark Eppler

Immunophilin-binding agents inhibit the phosphatase calcineurin, leading to the increased phosphorylation of certain brain proteins, including nitric oxide synthase. The increased levels of phosphorylation of nitric oxide synthase inhibits the enzymatic production of nitric oxide. Thus the neurotoxic effects of glutamate, which are ordinarily the result of vascular strokes and other neurodegenerative diseases, are minimized, because the neurotoxic effects are at least partially mediated by nitric oxide. Thus immunophilin-binding drugs can be used therapeutically in the treatment of vascular stroke and neurodegenerative disorders such as Alzheimer's disease and Huntington's disease.

Immunophilin-binding agents prevent glutamate neurotoxicity associated with vascular stroke and neurodegenerative diseases

Isolated DNA encoding mu-subtype opioid receptor polypeptides is provided. Recombinant cloning vectors which include this DNA and cells that incorporate these vectors are also provided. Methods for producing these receptors and purifying them from native and heterologous sources are also disclosed.

Mu-subtype opioid receptor

The cloning and characterization of a human dopamine transporter (HUDAT) cDNA is described. RFLP analysis is used to determine the distribution of HUDAT alleles in two ethic backgrounds. The means by which the association between HUDAT alleles and behavioral disorders which have altered HUDAT expression as a basis for their etiology is discussed. Methods for evaluating the expression of HUDAT are described.

Sequence of human dopamine transporter cDNA

The invention described in this disclosure relates to a cloned cDNA encoding the dopamine transporter protein usually found in certain neural cells. The invention is further directed to the purified dopamine transporter protein and its use as a biosensor material and immunogen for the production of anti-DAT1 antibodies. The disclosure also discusses methods for use of the cDNA for diagnostic and treatment applications, and methods for use of permanent cell lines transformed with the dopamine transporter cDNA for pharmaceutical screening. The use of anti-DAT1 antibodies as a diagnostic tool is also addressed.

CDNA encoding a dopamine transporter

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Towson, MD, United States of America

George R Uhl