Prokineticin polypeptides, related compositions and methods

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.

Description

[0001] This application claims the benefit of U.S. Provisional Application No. 60 / 245,882, filed Nov. 3, 2000, which is incorporated herein by reference.BACKGROUND OF THE INVENTION [0002] The main function of gastrointestinal (GI) smooth muscle is to mix and propel intralumenal contents, which enables efficient digestion of food, progressive absorption of nutrients, and eventual evacuation of residual components. The activity of GI smooth muscle is regulated by intrinsic and extrinsic neural signals, including classical neurotransmitters, co-existing neuropeptides, and circulating peptide hormones. In addition, a number of humoral agents including histamine, serotonin, and adenosine that are produced by nonneural GI cells also influence the activity of smooth muscle cells. [0003] A number of clinical conditions are associated with altered GI motility, including irritable bowel syndrome, diabetic gastroparesis, postoperational ileus, chronic constipation, gastrointestinal reflux dise...

AI Technical Summary

Benefits of technology

[0011] The invention also provides methods of identifying a prokineticin receptor ligand, by contacting a preparation containing prokineticin receptor with one or more candidate compounds, and identifying a compound that specifically binds to the receptor. Such a compound is characterized as a prokineticin receptor ligand.

[0012] Also provided are methods of identifying a prokineticin receptor agonist, by contacting a preparation containing a prokineticin receptor with one or more candidate compounds, and identifying a compound

Problems solved by technology

Methods of recombinantly preparing these snake and frog polypeptides, or of recombinantly preparing other polypeptides containing 10 cysteines, have not previously been described, limiting the utility of these regulators for therapeutic use.

Additionally, snake and frog polypeptides could elicit antibodies if administered to mammals that would likely reduce their efficacy as therapeutics.

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