Tent – canopy – umbrella – or cane – Umbrella – Self-opening and closing
Patent
1995-08-21
1999-01-19
LeGuyader, John L.
Tent, canopy, umbrella, or cane
Umbrella
Self-opening and closing
435 691, 4351723, 4353201, 536 231, 536 235, C12N 1585, C07H 2104
Patent
active
058613099
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
Throughout this application various publications are referred to by partial citations within parenthesis. Full citations for these publications may be found at the end of the specification immediately preceding the claims. The disclosures of these publications, in their entireties, are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.
Although adrenergic receptors (ARs) bind the same endogenous catecholamines (epinephrine and norepinephrine, NE) their physiological as well as pharmacological specificity is markedly diverse. This diversity is due primarily to the existence of at least nine different proteins encoding three distinct adrenergic receptors types (.alpha..sub.1, .alpha.2, and .beta.). These proteins belong to the super-family of G-protein coupled receptors, and are characterized by a single polypeptide chain which span the plasma membrane seven times, with an extracellular amino terminus, and a cytoplasmic carboxyl terminus. The molecular cloning of three genes encoding .alpha..sub.1 -ARs supports the existence of pharmacologically and anatomically distinct .alpha..sub.1 -receptor subtypes. The .alpha..sub.1b -receptor was originally cloned from a hamster smooth muscle cell line cDNA library, and encodes a 515 a.a. peptide that shows 42-47% homology with other ARs. The message for the .alpha..sub.1b -receptor is abundant in rat liver, heart, cerebral cortex and kidney, and its gene was localized to human chromosome 5 (4). A second cDNA clone from a bovine brain library was found which encoded a 466-residue polypeptide with 72% homology to the .alpha..sub.1b -AR gene. It was further distinguished from .alpha..sub.1b by the finding that its expression was restricted to human hippocampus, and by its localization to human chromosome 8 and it has been designated as the .alpha..sub.1c -AR (20). The cloning of an .alpha..sub.1a -AR has been reported recently. This gene, isolated from a rat brain cDNA library, encodes a 560-residue polypeptide that shows 73% homology with the hamster .alpha..sub.1b -receptor. The message for this subtype is abundant in rat vas deferens, aorta, cerebral cortex and hippocampus, and its gene has been localized to human chromosome 5 (12).
Pharmacological studies have demonstrated the existence of two .alpha..sub.1 -adrenergic receptor subtypes. The studies of .alpha..sub.1 -AR-mediated responses in vascular tissue suggested the possible existence of receptor subtypes, based on the potency and efficacy of adrenergic agonists, as well as differential sensitivity of .alpha..sub.1 receptor-mediated responses to extracellular calcium and calcium channel blockers (6, 24). Although radioligand binding studies of brain showed good agreement with the potency of .alpha.-adrenergic antagonists on vascular responses (23, 10), subsequent binding studies of rat brain .alpha..sub.1 -ARs provided strong evidence for the existence of receptor heterogeneity, based on the relative affinities for prazosin and WB4101 (15). These observations were supported by the finding that chloroethylclonidine (CEC) inactivated 50% of the .alpha..sub.1 sites from rat cerebral cortex and 80% of the binding sites from liver or spleen (.alpha..sub.1b), but did not inactivate .alpha..sub.1 -receptors from the hippocampus or vas deferens (.alpha..sub.1a) (14). Taken together, these results suggested a classification of the .alpha..sub.1a -subtype as high affinity for WB4101 and insensitive to alkylation by CEC, and .alpha..sub.1b -subtype as 10 to 20 fold lower affinity for WB4101, but sensitive to inactivation by CEC. Consistent with this evidence the transfection of the hamster .alpha..sub.1b gene into COS-7 cells induced the expression of an .alpha.1-receptor with high affinity for WB4101, 95% of which could be inactivated by CEC. Conversely, upon expression of the rat .alpha..sub.1a receptor gene in COS-7 cells, it showed a 10-fold higher affinity for WB4101 than the .alpha..sub.1b -recepto
REFERENCES:
patent: 4616017 (1986-10-01), Baldwin
patent: 4661491 (1987-04-01), Regnier
patent: 4873191 (1989-10-01), Wagner
patent: 5155128 (1992-10-01), Weinshank
Schwinn et al., Molecular cloning and expression of the cDNA for a novel alpha 1-adrenergic receptor subtype, J. Biol. Chem., vol. 265(14), pp. 8183-8189, May 1990.
Bruno et al., Molecular cloning and sequencing of a cDNA encoding a human alpha 1a adrenergic receptor, Biochem. Biophys. Res. Comm., vol. 179(3), pp. 1485-1490, Sep. 1991.
Cotecchia et al., Molecular cloning and expression of the cDNA for the hamster alpha 1-adrenergic receptor, Proc. Natl. Acad. Sci., vol. 85, pp. 7159-7163, Oct. 1988.
Lerner, R.A., Nature 1982 299:592-596.
Glover, D.M., Gene Cloning, Chapman & Hall, London 1984, pp. 1-20.
DiBona, G.F., FASEB 1989 3:1993-1994.
Yakubov, L.A., et al., Proc. Natl. Acad. Sci. USA 1989 86:6454-6458.
Cotton, M. and Birnstiel, M.L., EMBO J. 1989 8 (12):3861-3866.
Waspe, L.E. et al., J. Clin. Invest. 1990 85(4):1206-1214.
Voight, M.M., et al., Nucleic Acids. Res. 1990 18(4):1053.
Lomasney, L.W. et al., J. Biol. Chem. 266 (10):6365-6369.
Wagner, E. et al., Proc. Natl. Acad. Sci. USA 1991 88:4255-4259.
Bruno, J.F. et al., Biochem. Biophys. Res. Com. 1991 179(3):1485-1490.
Roemer, K. and Friedman T., Eur. J. Biochem. 1992 208:211-225.
Karson, E.M., et al., J. Reproduct. Med. 1992 37(6):508-514.
Schwinn, D.A., and Lomasney, J.W., Eur. J. Pharmacol. 1992 227(4):433-436.
Link, R., et al., Molec. Pharmacol. 1992 42:;16-27.
Adham, N., et al., Proc. Natl. Acad. Sci . USA 1993 90: 408-412.
Forray, C., et al., Molecular Pharmacol. 1994 45: 703-708.
Gao, et al., Gene 1993 131: 243-247.
Jones, C.R., et al., Progress In Brain Research 1991 88: 271-291.
Laz, T.M., et al., Molecular Pharmacol. 1994 46: 414-422.
Perala, M., et al., Molecular Brain Research 1992 16: 57-63.
Weinshank, R.L., et al., Proc. Natl. Acad. Sci. USA 1992 89: 3630-3634; and.
Yang-Feng, T.L., et al., Proc. Natl. Acad. Sci. USA 1990 87: 1516-1520.
Bard Jonathan A.
Forray Carlos
Weinshank Richard L.
LeGuyader John L.
Synaptic Pharmaceutical Corporation
Wang Andrew
White John P.
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