Brain-derived membrane-associated CRF binding proteins

Details Brain-derived membrane-associated CRF binding proteins Brain-derived membrane-associated CRF binding proteins

1993-11-08

1996-12-24

Walsh, Stephen G.

Chemistry: natural resins or derivatives; peptides or proteins;

Proteins, i.e., more than 100 amino acid residues

530306, C07K 14705, C07K 14695

Patent

active

055874622

ABSTRACT:
Isolated, substantially pure mammalian brain-derived membrane-associated CRF-binding proteins and biologically active fragments thereof are provided as well as isolated and purified DNA fragments which encode the CRF binding proteins or biologically active fragments thereof or homologs of other mammalian species. By administering an amount of such CRF binding protein or a fragment thereof effective to modulate receptor activation, it is possible to modulate the action of CRF upon (a) the brain and nervous system, (b) the pituitary particularly for production of ACTH, beta endorphin and cortisol, (c) sites of inflammation, (d) the placenta, (e) the adrenal glands, (f) the gonads or (g) the gastrointestinal tract. Administration of an N-terminal fragment of the protein increases the binding site density for CRF and thus modulates its biological effect in vivo.

REFERENCES:
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Behan et al., "Cloning and structure of the human corticotrophin releasing factor-binding protein gene (CRHBP)," Genomics 16:63-68 (1993).
De Souza, et al., "Corticotropin-releasing factor receptors in human pituitary gland: Autoradiographic localization," Neuroendocrinology 40:419-422 (1985).
Grigoriadis and De Souza, "The brain corticotropin-releasing factor (CRF) receptor is of lower apparent molecular weight than the CRF receptor in anterior pituitary," J. Bio. Chem. 263(22):10927-10931 (1988).
Grigoriadis, et al., "Solubilization of high affinity corticotropin-releasing factor receptors from rat brain: Characterization of an active digitonin-solubilized receptor complex," Endocrinology 125(6):3068-3077 (1989).
Potter, et al., "Cloning and characterization of the cDNAs for human and rat corticotropin releasing factor-binding proteins," Nature 349:423-426 (1991).
Potter et al., "The central distribution of a corticortropin-releasing factor (CFR)-binding protein predicts multiple sites and modes of interaction with CRF," P.N.A.S. 89:4192-4196 (1992).
Suda et al., "Corticotropin-releasing factor-binding protein is a glycoprotein," Biochem. Biophys. Res. Comm. 165(2):703-707 (1989).

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