Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1993-08-16
1997-11-25
Walsh, Stephen
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
435 691, 4352523, 43525411, 4353201, 435325, 530300, 530350, 536 235, 536 2431, C12N 1512, C07K 14435, C12Q 100
Patent
active
056911556
DESCRIPTION:
BRIEF SUMMARY
This application is a national phase application under 35 U.S.C. .sctn.371 of PCT application PCT/FR92/00023, filed Jan. 14, 1992.
The present invention relates to nucleotide sequences encoding the murine .beta.3-adrenergic receptor (RA.beta.3), to the use of the said sequences as probes and for the expression of peptides and/or fragments thereof which have a murine RA.beta.3 activity, to vectors useful for the said expression as well as to host cells containing the said vector.
The present invention also relates to polyclonal and monoclonal antibodies directed against the said peptides and which can be used especially for the detection of murine .beta.3-adrenergic receptors as well as to a process for screening substances with agonist or antagonist action towards peptides having a .beta.3-adrenergic receptor action, and to boxes or kits for the detection of the degree of affinity of various substances for the said peptides with .beta.3-adrenergic receptor activity. Such substances can especially be used as medicinal and products in the treatment of obesity, diabetes mellitus and diabetes of non-insulin-dependent subjects as well as in the treatment of hyperlipidemias.
BACKGROUND OF THE INVENTION
It is known that catecholamines such as adrenaline and noradrenaline, synthetic agonists of these catecholamines which mimic their biological functions, and antagonists which block these biological functions, exert their effects by binding to specific recognition sites (membrane receptors) situated on the cell membranes.
Two principal classes of adrenergic receptors have been defined, the .alpha.-adrenergic receptors and the .beta.-adrenergic receptors.
In both of these two classes, five subtypes of catecholamine receptors (.alpha.1, .alpha.2, .beta.1, .beta.2 and .beta.3-RA) can now be distinguished. Their genes were recently isolated and identified (S. COTECCHIA et al., 1988, Proc. Natl. Acad. Sci. USA, 85, 7159-7163; B. K. KOBILKA et al., 1987, Science, 238, 650-656; T. FRIELLE et al., 1987, Proc. Natl. Acad. Sci. USA 84, 7920-7924; L. J. EMORINE et al., 1987, Proc. Natl. Acad. Sci., USA, 84, 6995-6999; L. J. EMORINE et al., 1989, Science, 245, 1118-1121). Analysis of these genes has made it possible to recognise that they belong to a family of integral membrane receptors exhibiting some homology (R. A. F. DIXON et al., 1998, Annual Reports in Medicinal Chemistry, 221-223; L. J. Emorine et al., 1988, Proc. NATO Adv. Res. Workshop), especially at the level of 7 transmembrane regions which are coupled to regulatory proteins, called G proteins, capable of binding molecules of guanosine triphosphate (GTP).
These membrane receptors, after they have bound the appropriate ligand (agonist or antagonist), undergo a conformational change which induces an intracellular signal which modifies the behavior of the target cell. In the case of .beta.-adrenergic receptors, when they bind with agonists of catecholamines, they catalyse the activation of a class of G proteins which in turn stimulates the activity of adenylate cyclase whereas the antagonists of RA.beta. receptors act in competition with the agonists for the binding to the receptor and prevent the activation of adenylate cyclase.
When adenylate cyclase is activated, it catalyses the production of an intracellular mediator or second messenger, especially cyclic AMP.
SUMMARY OF THE INVENTION
A first aspect of the present invention is an isolated DNA molecule having the nucleotide sequence of SEQ ID NO:1 and encoding the murine .beta.3-adrenergic receptor protein.
A further aspect of the present invention is an isolated DNA molecule having the nucleotide sequence of SEQ ID NO:3.
A further aspect of the present invention is an isolated DNA molecule having the nucleotide sequence of SEQ ID NO:4, which sequence includes the coding region of the murine .beta.3-adrenergic receptor protein gene.
A further aspect of the present invention is an isolated DNA molecule of SEQ ID NO:6.
A further aspect of the present invention is an isolated DNA molecule of SEQ ID NO:7.
Anoth
REFERENCES:
patent: 5053337 (1991-10-01), Weinshank et al.
Cohen et al., Neurology, vol. 39 (Suppl. 1.), p. 388, 1989.
Baggott et al., Am. Rev. Respir. Dis., vol. 139, A366, 1989.
Lewin, Science, vol. 237, Sep. 25, 1987, p. 237.
Reeck et al., Cell, vol. 50, p. 667, 1987.
Nahmias, C. et al., "Molecular Characterization of the Mouse .beta.3-Adrenergic Receptor: Relationship with the Atypical Receptor of Adipocytes", The EMBO Journal, vol. 10, No. 12, pp. 3721-3727, 1991.
Emorine, Laurent J. et al., "Molecular Characterization of the Human .beta..sub.3 -Adrenergic Receptor", Science, vol. 245, pp. 1118-1120, Sep. 8, 1989.
Emorine et al., Science, v. 245, p. 1118, 1989.
Emorine Laurent Jean
Nahmias Clara
Strosberg Arthur Donny
Centre National De La Recherche Scientifigue
Teng Sally P.
Walsh Stephen
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