Cholinergic/serotoninergic receptor and uses thereof
View Patent ↗The present invention describes new cholinergic/serotoninergic chimeric receptors and provides methods and compositions suitable for screening for ligands such as agonists, antagonists and allosteric modulators of α7 nicotinic acetylcholine receptors.
1. A recombinant nucleic acid encoding a cholinergic/serotoninergic chimeric receptor, wherein the nucleic acid comprises SEQ ID NO:2.
2. The nucleic acid of claim 1 , wherein the nucleic acid encodes a polypeptide having an amino acid sequence as set forth in SEQ ID NO:10.
3. A vector comprising the recombinant nucleic acid of claim 1 .
4. The vector of claim 3 , wherein the recombinant nucleic acid is operably linked to control sequences recognized by a host cell transformed with the vector.
5. A host cell comprising the vector of claim 4 .
6. A method of producing a cholinergic/serotoninergic chimeric receptor comprising transforming a host cell with the vector of claim 3 .
7. A method for identifying a ligand to a cholinergic/serotoninergic chimeric receptor comprising the amino acid sequence of SEQ ID NO:10, wherein the method comprises contacting the cholinergic/serotoninergic chimeric receptor with a test compound, or a test compound and a positive allosteric modulator, and measuring a response of the cholinergic/serotoninergic chimeric receptor to the test compound, wherein a measurable response of the cell indicates that the test compound is a ligand to the cholinergic/serotoninergic chimeric receptor.
8. The method of claim 7 , wherein the cholinergic/serotoninergic chimeric receptor's response to the compound is measured by a binding assay or an electrophysiological assay.
9. The method of claim 7 , wherein the compound is selected from the group consisting of a human neuronal nicotinic cholinergic α7 agonist and a human neuronal nicotinic cholinergic α7 antagonist.
10. The method of claim 7 , wherein the positive allosteric modulator is a type I positive allosteric modulator or a type II positive allosteric modulator.