Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1995-02-21
1997-08-12
Walsh, Stephen
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
536 235, 536 2431, 435 691, 4352523, 43525411, 4353201, 435325, 435361, 530350, C12Q 100, C12N 1509, C07K 14705
Patent
active
056564406
DESCRIPTION:
BRIEF SUMMARY
This application was filed as application PCT/FR94/00447 on Apr. 21, 1994, and it entered the national stage on Feb. 21, 1995.
BACKGROUND OF INVENTION
1. Field of the Invention
The present invention relates to nucleotide sequences coding for the bovine .beta..sub.3 -adrenergic receptor (AR.beta..sub.3), to the use of the said sequences as probes and for the expression of peptides and/or of fragments of the latter having bovine AR.beta..sub.3 activity, to the vector which is useful for the said expression and also to host cells containing the said vector.
The present invention also relates to a method for the screening of substances possessing an agonist or antagonist action with respect to peptides of bovine origin having .beta..sub.3 -adrenergic receptor activity.
2. Description of the Related Art
Catecholamines such as adrenaline and noradrenaline, synthetic agonists of these catecholamines which mimic their biological functions and antagonists which block these biological functions are known to exert their effects by binding to specific recognition sites (membrane receptors) located on the cell membranes.
Two main classes of adrenergic receptors have been defined, .alpha.-adrenergic receptors and .beta.-adrenergic receptors.
In the set of these two classes, five subtypes of catecholamine receptors are now distinguished (.alpha..sub.1 -, .alpha..sub.2 -, .beta..sub.1 -, .beta..sub.2 - and .beta..sub.3 -AR). Their genes have recently been 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 enabled them to be recognized as belonging to a family of integral membrane receptors displaying certain homologies (R. A. F. DIXON et al., 1988, Annual Reports in Medicinal Chemistry, 221-233; L. J. EMORINE et al., 1988, Proc. NATO Adv. Res. Workshop), in particular in respect of 7 transmembrane regions which are coupled to regulatory proteins, known as G proteins, capable of binding guanosine triphosphate (GTP) molecules.
These membrane receptors, when they have bound the appropriate ligand (agonist or antagonist), undergo a change in conformation, which induces an intra-cellular signal which modifies the behaviour of the target cell.
In the case of .beta.-adrenergic receptors, when they bind to catecholamine agonists, they catalyse the activation of a class of G proteins, which in turn stimulates adenylate cyclase activity, while AR.beta. antagonists act in competition with the agonists for binding to the receptor and prevent activation of adenylate cyclase.
When adenylate cyclase is activated, it catalyses the production of an intracellular mediator or second messenger, in particular cyclic AMP.
The inventors have recently demonstrated new .beta.-adrenergic receptors in man, designated Hu-AR.beta..sub.3, and in the mouse (International Application WO 92/12,246), designated Mu-AR.beta..sub.3, and characterized by properties different from those of the .beta..sub.1 and .beta..sub.2 receptors, in particular in that they behave differently with respect to substances which are, respectively, .beta..sub.1 - and .beta..sub.2 -receptor antagonists and agonists (International Application WO 90/08,775).
In particular, the Hu-AR.beta..sub.3 receptor consists, more especially, of a sequence of 408 amino acids, and is considered to contain seven hydrophobic transmembrane regions separated by intra- and extracellular hydrophilic loops, and the Mu-AR.beta..sub.3 receptor consists of a sequence of 400 amino acids and also contains 7 transmembrane regions.
The previous studies relating to Hu-AR.beta..sub.3 and Mu-AR.beta..sub.3 showed, in particular, that the .beta..sub.3 -adrenergic receptor participates in disorders such as diabetes and/or obesity, in as much as it is expressed in tissues which play an important part i
REFERENCES:
Emorine et al., Science, vol. 245, pp. 1118-1121, 1989.
Nahmias et al., Embo Journal, vol. 10, pp. 3721-3727, 1991.
Casteilla et al., Biochemical J., vol. 297, Part 1, pp. 93-97, 1994.
Sambrook et al., Molecular Cloning, vol. 3, pp. 16.2-16.30 and 17.2-17.28, 1989, Cold Spring Harbor Lab. Press.
Benovic et al., Science, vol. 246, pp. 235-240, 1989.
Kapoor Archana
Lenzen Gerlinda
Teng Sally P.
Vetigen
Virbac
Walsh Stephen
LandOfFree
Nucleotide sequences coding for the bovine .beta..sub.3 -adrener does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Nucleotide sequences coding for the bovine .beta..sub.3 -adrener, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nucleotide sequences coding for the bovine .beta..sub.3 -adrener will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-159311