Abstract: In alternative embodiments, provided are methods for: modifying circadian rhythmicity or timing in a mammal, treating psychiatric conditions or symptoms due to alterations in a human circadian regulatory system, treating sleep problems in a mammal, or inducing sleep or activity suppression, or causing an arousal or wakening reaction, comprising administration to a mammal or human a compound or composition capable of modifying a prokineticin 2 (PK2) expression or activity, and/or a PKR2 (PK2 receptor), a vasopressin receptor (VR), and/or a melatonin receptor (MR) expression or activity.

Abstract: In alternative embodiments, provided are methods for: modifying circadian rhythmicity or timing in a mammal, treating psychiatric conditions or symptoms due to alterations in a human circadian regulatory system, treating sleep problems in a mammal, or inducing sleep or activity suppression, or causing an arousal or wakening reaction, comprising administration to a mammal or human a compound or composition capable of modifying a prokineticin 2 (PK2) expression or activity, and/or a PKR2 (PK2 receptor), a vasopressin receptor (VR), and/or a melatonin receptor (MR) expression or activity.

Abstract: Contemplated compounds, compositions, and methods of prokineticin antagonists are presented where a prokineticin antagonist is used in the treatment and prevention of various conditions and disorders, and especially type II diabetes.

Abstract: Contemplated compounds, compositions, and methods of prokineticin antagonists are presented where a prokineticin antagonist is used in the treatment and prevention of various conditions and disorders, and especially type II diabetes.

Abstract: The present invention relates to a method of identifying agents that modulate prokineticin receptors, particularly, in the brain. Such agents are useful in the treatment of cerebrovascular diseases, including cerebral ischemia, cerebral hemorrhage, ischemic stroke, hemorrhagic stroke, and ischemic reperfusion injury. Additionally, such agents are useful to treat seizure disorders, such as epilepsy.

Abstract: The invention is based on the discovery that an effective therapeutic strategy for ameliorating the symptoms of anxiety-related disorders can be achieved by decreasing levels of PK2 and administering an effective amount of PK2 receptor antagonist. A method of modulating the behavioral response of a subject displaying symptoms of stress responses and/or anxiety-related disorders is disclosed. The disclosed methods indicate that PK2 is an essential regulator of behavioral stress response independent of HPA.

Abstract: The invention provides a method for screening for a compound for modulating circadian rhythm. The method involves (a) providing a compound that is a Prokineticin 2 (PK2) receptor antagonist or agonist; and (b) determining the ability of the compound to modulate one or more indicia of circadian rhythm function, wherein a compound that modulates one or more indicia of circadian rhythm function is identified as a compound for modulating circadian rhythm. The invention also provides a mouse PK2 receptor nucleic acid, polypeptide and related compositions. Further provided is a method for modulating circadian rhythm of an animal, which involves administering an effective amount of a PK2 receptor antagonist or agonist to an animal. Also provided is an isolated nucleic acid comprising a PK2 gene promoter operatively linked to a heterologous nucleotide sequence.

Abstract: The invention provides methods of identifying compounds that modulate neurogenesis. The methods involve providing a compound that modulates prokineticin receptor signaling; contacting a neural stem or progenitor cell with the compound; and determining the ability of the compound to modulate neurogenesis. The invention also provides methods for modulating neurogenesis. The methods involve contacting a neural stem or progenitor cell with an effective amount of a compound that modulates prokineticin receptor signaling. Such methods are useful for both ex vivo or in vivo therapeutic applications where neural regeneration is desirable.

Abstract: The invention provides an isolated squirrel monkey prokineticin receptor 2 (PKR2) polypeptide containing the amino acid sequence referenced as SEQ ID NO:2. The invention also provides an isolated chimpanzee PKR2 containing the amino acid sequence referenced as SEQ ID NO:4. Also provided are methods of identifying PKR2 agonists and antagonists using the squirrel monkey PKR2 polypeptide. Additionally, the invention provides an isolated rhesus monkey PK2 polypeptide containing the amino acid sequence referenced as SEQ ID NO:6. Nucleic acid molecules encoding the disclosed polypeptides further are provided by the invention.

Abstract: The invention provides methods of modulating gastric acid secretion by administering an amount of a prokineticin receptor antagonist effective to alter one or more indicia of gastric acid secretion, wherein the antagonist contains an amino acid sequence at least 80% identical to amino acids to 7 to 77 of SEQ ID NO:3, which includes (a) the 10 conserved cysteine residues of SEQ ID NO:3, and (b) from 0 to 9 of amino acids 78 to 86 of SEQ ID NO:3, wherein amino acids 1 to 6 of the antagonist do not consist of amino acids AVITGA (SEQ ID NO:21). In another embodiment, the antagonist contains an amino acid sequence at least 80% identical to amino acids to 7 to 77 of SEQ ID NO:6, which includes (a) the 10 conserved cysteine residues of SEQ ID NO:6, and (b) from 0 to 4 of amino acids 78 to 81 of SEQ ID NO:6, wherein amino acids 1 to 6 of the antagonist do not consist of amino acids AVITGA (SEQ ID NO:21).

Abstract: The invention provides methods of modulating gastric acid secretion by administering an amount of a prokineticin receptor antagonist effective to alter one or more indicia of gastric acid secretion, wherein the antagonist contains an amino acid sequence at least 80% identical to amino acids to 7 to 77 of SEQ ID NO:3, which includes (a) the 10 conserved cysteine residues of SEQ ID NO:3, and (b) from 0 to 9 of amino acids 78 to 86 of SEQ ID NO:3, wherein amino acids 1 to 6 of the antagonist do not consist of amino acids AVITGA (SEQ ID NO:21). In another embodiment, the antagonist contains an amino acid sequence at least 80% identical to amino acids to 7 to 77 of SEQ ID NO:6, which includes (a) the 10 conserved cysteine residues of SEQ ID NO:6, and (b) from 0 to 4 of amino acids 78 to 81 of SEQ ID NO:6, wherein amino acids 1 to 6 of the antagonist do not consist of amino acids AVITGA (SEQ ID NO:21).

Abstract: The invention provides a method for screening for a compound for modulating circadian rhythm. The method involves (a) providing a compound that is a Prokineticin 2 (PK2) receptor antagonist or agonist; and (b) determining the ability of the compound to modulate one or more indicia of circadian rhythm function, wherein a compound that modulates one or more indicia of circadian rhythm function is identified as a compound for modulating circadian rhythm. The invention also provides a mouse PK2 receptor nucleic acid, polypeptide and related compositions. Further provided is a method for modulating circadian rhythm of an animal, which involves administering an effective amount of a PK2 receptor antagonist or agonist to an animal. Also provided is an isolated nucleic acid comprising a PK2 gene promoter operatively linked to a heterologous nucleotide sequence.

Abstract: The invention provides isolated polypeptides that stimulate gastroeintestinal smooth muscle contraction, including human prokineticin 1 and human prokineticin 2 polypeptides, and functional fragments and modifications thereof. Also provided are methods of stimulating gastrointestinal smooth muscle contraction in a mammal, by administering to the mammal an effective amount of a prokineticin polypeptide. The invention also provides nucleic acid molecules encoding a prokineticin polypeptide, and antibodies that selectively bind a prokineticin polypeptide. Further provided are methods of identifying a prokineticin receptor ligand, agonist or antagonist.

Abstract: The invention provides isolated polypeptides that stimulate gastrointestinal smooth muscle contraction, including human prokineticin 1 and human prokineticin 2 polypeptides, and functional fragments and modifications thereof. Also provided are methods of stimulating gastrointestinal smooth muscle contraction in a mammal, by administering to the mammal an effective amount of a prokineticin polypeptide. The invention also provides nucleic acid molecules encoding a prokineticin polypeptide, and antibodies that selectively bind a prokineticin polypeptide. Further provided are methods of identifying a prokineticin receptor ligand, agonist or antagonist.

Abstract: The invention provides an isolated squirrel monkey prokineticin receptor 2 (PKR2) polypeptide containing the amino acid sequence referenced as SEQ ID NO:2; an isolated chimpanzee PKR2 containing the amino acid sequence referenced as SEQ ID NO:4; and an isolated rhesus monkey prokineticin receptor 1 (PKR1) referenced as SEQ ID NO:30. Also provided are methods of identifying PKR1 and PKR2 agonists and antagonists using the newly identified PKR2 and PKR1 polypeptides. Additionally, the invention provides an isolated rhesus monkey PK2 polypeptide containing the amino acid sequence referenced as SEQ ID NO:6, and an isolated rhesus monkey PK1 polypeptide containing the amino acid sequence referenced as SEQ ID NO:28. Nucleic acid molecules encoding the disclosed polypeptides further are provided by the invention.

Abstract: The invention provides an isolated prokineticin receptor 2 long isoform polypeptide that contains an amino acid sequence selected from the amino acid sequences referenced as SEQ ID NO:2, SEQ ID NO:3, or SEQ ID NO:4. Also provided is an isolated prokineticin receptor 2 short isoform polypeptide, which contains the amino acid sequence referenced as SEQ ID NO:5. Also provided is further prokineticin 2 short isoform polypeptide containing the sequence of SEQ ID NO:17. Further provided is an isolated prokineticin receptor 1 short isoform polypeptide that contains the amino acid sequence referenced as SEQ ID NO:6. The invention also provides methods for preparing an isolated polypeptide corresponding to a long or short PKR isoform of the invention; as well as antibodies That selectively bind to a long or short PKR isoform of the invention. Methods for identifying agonists and antagonists of PKR1 and PKR2 further are provided by the invention.

Abstract: The invention provides an isolated squirrel monkey prokineticin receptor 2 (PKR2) polypeptide containing the amino acid sequence referenced as SEQ ID NO:2. The invention also provides an isolated chimpanzee PKR2 containing the amino acid sequence referenced as SEQ ID NO:4. Also provided are methods of identifying PKR2 agonists and antagonists using the squirrel monkey PKR2 polypeptide. Additionally, the invention provides an isolated rhesus monkey PK2 polypeptide containing the amino acid sequence referenced as SEQ ID NO:6. Nucleic acid molecules encoding the disclosed polypeptides further are provided by the invention.

Abstract: The invention provides isolated polypeptides that stimulate gastroeintestinal smooth muscle contraction, including human prokineticin 1 and human prokineticin 2 polypeptides, and functional fragments and modifications thereof. Also provided are methods of stimulating gastrointestinal smooth muscle contraction in a mammal, by administering to the mammal an effective amount of a prokineticin polypeptide. The invention also provides nucleic acid molecules encoding a prokineticin polypeptide, and antibodies that selectively bind a prokineticin polypeptide. Further provided are methods of identifying a prokineticin receptor ligand, agonist or antagonist.

Abstract: The invention provides isolated polypeptides that stimulate gastrointestinal smooth muscle contraction, including human prokineticin 1 and human prokineticin 2 polypeptides, and functional fragments and modifications thereof. Also provided are methods of stimulating gastrointestinal smooth muscle contraction in a mammal, by administering to the mammal an effective amount of a prokineticin polypeptide. The invention also provides nucleic acid molecules encoding a prokineticin polypeptide, and antibodies that selectively bind a prokineticin polypeptide. Further provided are methods of identifying a prokineticin receptor ligand, agonist or antagonist.

Abstract: The invention provides methods of modulating gastric acid secretion by administering an amount of a prokineticin receptor antagonist effective to alter one or more indicia of gastric acid secretion, wherein the antagonist contains an amino acid sequence at least 80% identical to amino acids to 7 to 77 of SEQ ID NO:3, which includes (a) the 10 conserved cysteine residues of SEQ ID NO:3, and (b) from 0 to 9 of amino acids 78 to 86 of SEQ ID NO:3, wherein amino acids 1 to 6 of the antagonist do not consist of amino acids AVITGA (SEQ ID NO:21). In another embodiment, the antagonist contains an amino acid sequence at least 80% identical to amino acids to 7 to 77 of SEQ ID NO:6, which includes (a) the 10 conserved cysteine residues of SEQ ID NO:6, and (b) from 0 to 4 of amino acids 78 to 81 of SEQ ID NO:6, wherein amino acids 1 to 6 of the antagonist do not consist of amino acids AVITGA (SEQ ID NO:21).