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Home Drugs DNA-encoding-5-HT-sub-4-serotonin-receptors-and-uses-thereof

 DNA encoding 5-HT.sub.4 serotonin receptors and uses thereof

Details
Inventors: Gerald, Christophe; Hartig, Paul R.; Branchek, Theresa; Weinshank, Richard L.;
Assignee: Synaptic Pharmaceutical Corporation (Paramus, NJ)
Primary Examiner: Allen; Marianne P.
Assistant Examiner:
Attorney, Agent or Firm: White; John P. Cooper & Dunham LLP

This invention provides an isolated nucleic acid molecule encoding a mammalian 5-HT.sub.4 receptor and an isolated nucleic acid molecule encoding a human 5-HT.sub.4 receptor, an isolated protein which is a mammalian 5-HT.sub.4 receptor, an isolated protein which is a human 5-HT.sub.4 receptor, vectors comprising an isolated nucleic acid molecule encoding a mammalian 5-HT.sub.4 receptor, vectors comprising an isolated nucleic acid molecule encoding a human 5-HT.sub.4 receptor, mammalian cells comprising such vectors, antibodies directed to the 5-HT.sub.4 receptor, nucleic acid probes useful for detecting nucleic acid encoding a mammalian or human 5-HT.sub.4 receptor, antisense oligonucleotides complementary to any sequences of a nucleic acid molecule which encodes a mammalian or human 5-HT.sub.4 receptor, pharmaceutical compounds related to the human 5-HT.sub.4 receptor, and nonhuman transgenic animals which express DNA encoding a normal or a mutant mammalian or human 5-HT.sub.4 receptor. This invention further provides methods for determining ligand binding, detecting expression, drug screening, and treatments for alleviating abnormalities associated with a human 5-HT.sub.4 receptor.

DETAILED DESCRIPTION OF THE INVENTION This invention provides an isolated nucleic acid molecule encoding a mammalian 5-HT.
sub.
4 receptor.
This invention further provides an isolated nucleic acid molecule encoding a human 5-HT.
sub.
4 receptor.
As used herein, the term "isolated nucleic acid molecule" means a non-naturally occurring nucleic acid molecule that is, a molecule in a form which does not occur in nature.
Examples of such an isolated nucleic acid molecule are an RNA, cDNA, or isolated genomic DNA molecule encoding a mammalian 5-HT.
sub.
4 receptor or a human 5-HT.
sub.
4 receptor.
As used herein, "5-HT.
sub.
4 receptor" means a molecule which, under physiologic conditions, is substantially specific for the neurotransmitter serotonin, is saturable, of high affinity for serotonin and the activation of which is coupled to the activation of adenylate cyclase and the "5-HT.
sub.
4 receptor" is also sensitive to benzamide derivatives which act as agonists and partial agonists at this receptor subtype.
One embodiment of this invention is an isolated nucleic acid molecule encoding a mammalian 5-HT.
sub.
4 receptor.
Such a molecule may have coding sequences substantially the same as the coding sequences shown in FIGS.
1 and 2 and 5 (SEQ ID NOs.
1, 3 and 5).
A preferred embodiment is an isolated nucleic acid molecule encoding a human 5-HT.
sub.
4 receptor.
Such a molecule may have a coding sequence substantially the same as the coding sequence shown in FIG.
5 (SEQ ID NO.
5).
The DNA molecules of FIGS.
1, 2 and 5 (Seq ID NOs.
1, 3 and 5) encode the sequence of mammalian 5-HT.
sub.
4 receptors.
The DNA molecule of FIG.
5 (Seq ID No.
5) encodes a human 5-HT.
sub.
4 receptor.
This invention further provides isolated DNA molecules encoding mammalian 5-HT.
sub.
4 receptors having the sequence H.
sub.
2 N--Y--X--COOH wherein Y is the amino acid sequence beginning at amino acid 1 and ending at amino acid 359 of FIG.
1 (SEQ ID NOs.
1 and 2) and wherein X is an amino acid sequence encoding the carboxy terminal region of the receptor



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