Abstract: The present invention relates to rapid, quantitative, specific, high through-put methods for screening test substances for their ability to inhibit activity of an ouabain-resistant Na+—K+-ATPase involved in a variety of biological processes such as regulation of osmotic balance and cell volume, maintenance of the resting membrane potential, establishment of the ionic composition of cerebrospinal fluid and aqueous humor, electrical activity of muscle and nerve, and receptor-mediated endocytosis, cardiac muscle contractility, neurotransmitter metabolism and vascular muscle cell contraction. These methods can be employed to identify compounds for use in therapeutic applications for disease processes in which dysfunction of the Na+—K+-ATPase contributes to a pathological process. The present invention also includes kits which are used in the methods provided herein.

Abstract: The invention relates to a monoclonal antibody or antigen binding fragment thereof having binding specificity for ouabain, wherein the antibody or antigen binding fragment does not crossreact with digoxin. Preferably the anti-ouabain monoclonal antibody can bind ouabain with an affinity of at least about 10?7M, preferably 10?8M, and more preferably 10?9M. The invention also relates to diagnostic and therapeutic uses of the monoclonal antibodies described herein.

Abstract: The present invention relates to a method of isolating and/or purifying hypothalamic inhibitory factor (HIF) from a sample (e.g., tissue fluid) containing HIF. The present invention provides for isolation of large amounts of HIF using diafiltration, solid phase extraction and immunoaffinity techniques. In one embodiment, the invention relates to a method of purifying hypothalamic inhibitory factor from a sample containing hypothalamic inhibitory factor comprising subjecting the sample to diafiltration, solid phase extraction and immunoaffintiy chromatography.

Abstract: The present invention relates to rapid, quantitative, specific, high through-put methods for screening test substances for their ability to inhibit activity of an ouabain-resistant Na+-K+-ATPase involved in a variety of biological processes such as regulation of osmotic balance and cell volume, maintenance of the resting membrane potential, establishment of the ionic composition of cerebrospinal fluid and aqueous humor, electrical activity of muscle and nerve, and receptor-mediated endocytosis, cardiac muscle contractility, neurotransmitter metabolism and vascular muscle cell contraction. These methods can be employed to identify compounds for use in therapeutic applications for disease processes in which dysfunction of the Na+-K+-ATPase contributes to a pathological process. The present invention also includes kits which are used in the methods provided herein.

Abstract: The present invention relates to rapid, quantitative, specific, high through-put methods for screening test substances for their ability to inhibit activity of an ouabain-resistant Na+-K+-ATPase involved in a variety of biological processes such as regulation of osmotic balance and cell volume, maintenance of the resting membrane potential, establishment of the ionic composition of cerebrospinal fluid and aqueous humor, electrical activity of muscle and nerve, and receptor-mediated endocytosis, cardiac muscle contractility, neurotransmitter metabolism and vascular muscle cell contraction. These methods can be employed to identify compounds for use in therapeutic applications for disease processes in which dysfunction of the Na+-K+-ATPase contributes to a pathological process. The present invention also includes kits which are used in the methods provided herein.

Abstract: The present invention relates to a method of identifying an agent (e.g., peptide, small molecule) that alters (partially, completely) the activity (function, expression) of HIF. In one embodiment, the method of identifying an agent that alters (e.g., inhibits, enhances) the activity of HIF comprises contacting a molecule in the HIF biosynthetic pathway (e.g., a precursor of HIF, such as a steroid precursor; an enzyme) with an agent to be assessed and determining whether the activity of the molecule (function, expression) is altered in the presence of the agent when compared to the activity of the molecule in the absence of the agent. The invention is also related methods of treatment using such agents; and methods of monitoring the biosynthetic pathway of OLC/HIF. In particular, the invention is related to agents, treatments, and diagnostics for diseases such as hypertension and heart failure.

Abstract: The present invention is based on the unexpected discoveries that hypothalamic inhibitory factor (HIF) has a positive inotropic effect in a whole organ preparation, such as an isolated perfused heart, and that HIF, to a greater extent than ouabain, dilates the coronary arteries in the isolated perfused heart as manifested in increased coronary flow in hearts treated with HIP. The present invention relates to a method for increasing coronary perfusion in a mammalian host comprising administering to the host in need thereof an effective amount of hypothalamic inhibitory factor (HIF). The invention also relates to a method for producing an increased coronary vasodilatory effect in a mammalian host comprising administering to a mammalian host in need thereof an effective amount of HIF. The method of the present invention can be used to prevent and/or treat ischemic cardiac malfunction and coronary artery restenosis.

Abstract: The present invention is based on the unexpected discoveries that hypothalamic inhibitory factor (HIF) has a positive inotropic effect in a whole organ preparation, such as an isolated perfused heart, and that HIF, to a greater extent than ouabain, dilates the coronary arteries in the isolated perfused heart as manifested in increased coronary flow in hearts treated with HIF. The present invention relates to a method for increasing coronary perfusion in a mammalian host comprising administering to the host in need thereof an effective amount of hypothalamic inhibitory factor (HIF). The invention also relates to a method for producing an increased coronary vasodilatory effect in a mammalian host comprising administering to a mammalian host in need thereof an effective amount of HIF. The method of the present invention can be used to prevent and/or treat ischemic cardiac malfunction and coronary artery restenosis.