Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1997-07-25
1999-08-17
Guzo, David
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
435 71, 435 72, 435 721, 435 691, 4353201, 435326, 435365, 435352, 435363, 435366, 435358, 536 235, 536 245, C12Q 168, C12Q 102, C12N 1585, C12N 510
Patent
active
059392630
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
Neuropeptide Y (NPY) is a 36 residue, amidated polypeptide. It is anatomically co-distributed and co-released with norepinephrine in and Stimulation of the sympathetic nervous system under physiological cardiogenic shock are associated with probable releases of NPY into the
At the cellular level, neuropeptide Y binds to a G-protein coupled receptor When administered intracerebroventricularly or injected into the hypothalamic paraventricular nucleus (PVN) it elicits eating in satiated effects on energy metabolism include decreased thermogenesis, body temperature and uncoupling protein, and increased white fat storage and acting antagonist for the appropriate NPY receptor subtype may be therapeutically useful for treating obesity and diabetes. Other disorders which might be targeted therapeutically include anxiety, hypertension, cocaine withdrawal, congestive heart failure, memory enhancement, cardiac and cerebral vasospasm, pheochromocytoma and ganglioneuroblastoma, and
At least four receptor subtypes of the NPY family have been proposed based on pharmacological and physiological properties. The Y1 receptor is stimulated by NPY or PYY (peptide YY) and appears to be the major vascular C-terminal fragments of NPY or PYY and is abundantly expressed both is exclusively responsive to NPY and is likely present in adrenal medulla, receptor family are known to exist, based on pharmacological and behavior is stimulated potently by NPY, NPY.sub.2-36 and the Y.sub.1 characteristic of the defined Y1, Y2 or Y3 receptors and can thus be that is responsible for evoking the feeding response. In addition, data indicate the existence of additional members of this receptor family affinity for short C-terminal fragments of NPY which induce hypotension associated with binding of NPY and PYY to brain sigma and phencyclidine
The Y1 receptor has been cloned and shown to be a G-protein coupled of a novel NPY receptor, other NPY receptors had not been cloned.
REFERENCES
immunoreactivity in the rat central nervous system--II. Immunohistochemical analysis. Neuroscience, 1986. 18(3): p. 545-618. during physical exercise in man. Biochem Biophys Res Comrnun, 1985. 133(1): p. 30-6. during sympathetic activation in man. J Auton Nerv Syst, 1986. 17(2): p. 143-9. noradrenaline in peripheral sympathetic vascular control. Acta Physiol Scand Suppl, 1988. 568(1): p. 1-56. immunoreactivity in brainstem catecholaminergic neurons that project to the paraventricular nucleus of the hypothalamus. J Comp Neurol, 1985. 241(2): p. 138-53. vasoconstrictor cooperation in vivo and in vitro. Am J Physiol, 1990. 258: p. R736-R742. noradrenaline from the human heart during exercise and hypoxia. Clin Physiol, 1990. 10(2): p. 179-88. similar hypothalamic neuropeptide Y increases in rats. Am J Physiol, 1993. 264: p. E279-E284. Neuropeptide- Y levels in acute Cold-Exposed rats. Neuroscience, 1993. 54(1): p. 127-132. cardiovascular responses to stress. Synapse, 1988. 2(3): p. 293-8. produced by food deprivation and for a variant of the Y1 receptor mediating this peptide's effect. Peptides, 1992. 13: p. 581-587. eating behavior, endocrine, and autonomic systems for body energy balance, in Neuropeptide Y, W. F. Colmers and C. Wahlestedt, Editor. 1993, Humana Press: Totowa, N.J. p. 457-509. relaxation, and membrane potential of rabbit cerebral arteries. J Cardiovasc Pharmacol, 1989. 13(1): p. 52-63. inhibits relaxation of rabbit coronary arteries. J Cardiovasc Pharmacol, 1987. 9(6): p. 675-81. Y in anesthetized rats. Eur J Pharmacol, 1990. 179(1-2): p. 83-7. receptors. Br J Pharmacol, 1992. 105(1): p. 45-50. cell-dependent vasodepressor agents. Eur. J. Pharmacol., 1993. 204: p. 249-256. brainstem nuclei. Circ Res, 1989. 64(1): p. 55-61. of neuropeptide Y in the nucleus tractus solitarius of rats: relationship with noradrenaline and vasopressin. Peptides, 1985. 6(3): p. 421-5. atypical receptor to evoke cardiovascular depression and to inhibit glutamate responsiveness in the brainstem. J Pharmacol Exp Ther, 1991. 258(2): p. 633-8. of the
REFERENCES:
Neuropeptide Y effector systems: perspectives for drug development.
C.J. Billington & A.S. Levine, Neurobiology, 1992, 2:847-851, entitled Hypothalamic neuropeptide Y regulation of feeding and energy metabolism.
A.S. Levine & J.E. Morley, Peptides, 1984, 5:1025-1029, entitled Neuropeptide Y: A Potent Inducer of Consummatory Behavior in Rats.
Grundemar, L., et al., Characterization of vascular neuropeptide Y receptors Br. J. Pharmacol. 1992.105 (1):pp. 45-50.
Wahlestedt, C., et al., Evidence for different pre- and post-junctional receptors for neuropeptide Y and related peptides, Regul. Pept. 1986.13 (3-4):pp. 307-318.
Jorgensen et al., Structure-function studies on neuropeptide Y and pancreatic polypeptide--evidence for two PP-fold receptors in vas deferens, Eur. J. Pharmacol. 1990. 186 (1): pp. 105-114.
Cox, H.M., et al., The Effects of Selective Amino Acid Substitution Upon Neuropeptide Y Antisecretory Potency in rat Jejunum Mucosa, Peptides, 1991, 12(2):pp. 323-327.
Wahlestedt, C., et al., Identification of Cultured Cells Selectivity Expressing Y1-, Y2-, or Y3-Type Receptors for Neuropeptide Y/Peptide YY, Life Sciences, 1992, 50:pp. PL7-PL12.
Balasubrananian, A., et al., Characterization of Neuropeptide Y Binding Sites in Rat Cardiac Ventricular Membranes 1, Peptides 1990. 11(3):pp. 545-550.
Li, X.J., et al., Cloning, Functional Expression, and Developmental Regulation of a Neuropeptide Y Receptor from Drosophila Melangaster*, J. Biol. Chem., 1992. 267(1):pp. 9-12.
Jolicoeur, F.B., In Vivo Structure Activity Study Supports the Existence of Heterogeneous Neuropeptide Y Receptors, Brain Res. Bull., 1991. 26(2):pp. 309-311.
Liebowitz & Alexander, Analysis of Neuropeptide Y-Induced Feeding: Dissociation of Y1 and Y2 Receptor Effects on Natural Meal Patterns, Peptides, 1991. 12(6):pp. 1251-1260.
B.G. Stanley, et al., Peptides, 1992, 13:581-587,entitled Evidence for Neuropeptide Y Mediation of Eating Produced by Food Deprivation and for a Variant of the Y1 Receptor Mediating This Peptide's Effect.
H. Herzog, et al., Proc. Natl. Acad. Sci., 1992, 89:5794-5798, entitled Cloned human neuropeptide Y receptor couples to two different messenger system.
D. Larhammar, et al., J. Biol. Chem., 1992, 267(16):10935-10938, entitled Cloning and Functional Expression of a Human Neuropeptide Y/Peptide YY Receptor of the Y1 Type.
C. Eva, et al., FEBS, 1990, vol. 271, No. 1, 2, 81-84, entitled Molecular cloning of a novel G protein-coupled receptor that may belong to the neuropeptide receptor family.
C. Wahlestedt & D.J. Reis, Annu. Rev. Pharmacol. Toxicol., 1993, 32:309-352, entitled Neuropeptide Y-Related Peptides and their Receptors--Are the Receptors Potential Therapeutic Drug Targets?.
Strader, C.D., I.S. Sigal, and R.A. Dixon, Structural basis of .beta.-adrenergic recptor function. FASEB-J, 1989. 3(7): pp. 1825-1832.
Dube, M. G., et al., Evidence that neuropeptide-Y is a physiological signal for normal food-intake, Brain Research, 1994, 646:341-344.
Sasaki et al., Nature, vol. 351, pp. 230-233 (1991).
Kluxen et al., PNAS, vol. 89, pp. 4618-4622 (1992).
Cohen et al., DNA and Cell Biology, "Characterization of a Mouse b1-Adrenergic Receptor . . . ", vol. 12(6), pp. 537-547 (1993).
Cascieri Margaret A.
Linemeyer David L.
MacNeil Douglas J.
Shiao Lin-Lin
Strader Catherine D.
Guzo David
Merck & Co., Ltd.
Windokur Melvin
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