Diagnostics and therapeutics for diseases associated with 5-hydroxytryptamine 2a receptor (5ht2a)
The invention provides a human 5HT2a which is associated with the cardiovascular diseases, respiratory diseases, dermatological diseases, gastroenterological diseases, cancer, inflammation, metabolic diseases, hematological diseases, muscle skeleton diseases, neurological diseases, urological diseases. The invention also provides assays for the identification of compounds useful in the treatment or prevention of cardiovascular diseases, respiratory diseases, dermatological diseases, gastroenterological diseases, cancer, inflammation, metabolic diseases, hematological diseases, muscle skeleton diseases, neurological diseases, urological diseases. The invention also features compounds which bind to and/or activate or inhibit the activity of 5HT2a as well as pharmaceutical compositions comprising such compounds.
1 . A method of screening for therapeutic agents useful in the treatment of a disease selected from the group consisting of cardiovascular diseases, respiratory diseases, dermatological diseases, gastroenterological diseases, cancer, inflammation, metabolic diseases, hematological diseases, muscle skeleton diseases, neurological diseases, and urological diseases in a mammal, comprising the steps of
i) contacting a test compound with a 5HT2a polypeptide, and
ii) detecting binding of said test compound to said 5HT2a polypeptide.
2 . A method of screening for therapeutic agents useful in the treatment of a disease selected from the group consisting of cardiovascular diseases, respiratory diseases, dermatological diseases, gastroenterological diseases, cancer, inflammation, metabolic diseases, hematological diseases, muscle skeleton diseases, neurological diseases and urological diseases in a mammal, comprising the steps of
i) determining activity of a 5HT2a polypeptide at a certain concentration of a test compound or in the absence of said test compound, and
ii), determining the activity of said polypeptide at a different concentration of said test compound.
3 . A method of screening for therapeutic agents useful in the treatment of a disease consisting of cardiovascular diseases, respiratory diseases, dermatological diseases, gastroenterological diseases, cancer, inflammation, metabolic diseases, hematological diseases, muscle skeleton diseases, neurological diseases and urological diseases in a mammal, comprising the steps of
i) determining the activity of a 5HT2a polypeptide at a certain concentration of a test compound, and
ii) determining the activity of a 5HT2a polypeptide at the presence of a compound known to be a regulator of a 5HT2a polypeptide.
4 . The method of claim 1 , wherein the step of contacting is in or at the surface of a cell.
5 . The method of claim 1 , wherein the cell is in vitro.
6 . The method of claim 1 , wherein the step of contacting is in a cell-free system.
7 . The method of claim 1 , wherein the polypeptide is coupled to a detectable label.
8 . The method of claim 1 , wherein the compound is coupled to a detectable label.
9 . The method of claim 1 , wherein the test compound displaces a ligand which is first bound to the polypeptide.
10 . The method of claim 1 , wherein the polypeptide is attached to a solid support.
11 . The method of claim 1 , wherein the compound is attached to a solid support.
12 . A method of screening for therapeutic agents useful in the treatment of a disease selected from the group consisting of cardiovascular diseases, respiratory diseases, dermatological diseases, gastroenterological diseases, cancer, inflammation, metabolic diseases, hematological diseases, muscle skeleton diseases, neurological diseases and urological diseases in a mammal, comprising the steps of
i) contacting a test compound with a 5HT2a polynucleotide, and
ii) detecting binding of said test compound to said 5HT2a polynucleotide.
13 . The method of claim 12 wherein the nucleic acid molecule is RNA.
14 . The method of claim 12 wherein the contacting step is in or at the surface of a cell.
15 . The method of claim 12 wherein the contacting step is in a cell-free system.
16 . The method of claim 12 wherein polynucleotide is coupled to a detectable label.
17 . The method of claim 12 wherein the test compound is coupled to a detectable label.
18 . A method of diagnosing a disease selected from the group consisting of cardiovascular diseases, respiratory diseases, dermatological diseases, gastroenterological diseases, cancer, inflammation, metabolic diseases, hematological diseases, muscle skeleton diseases, neurological diseases, and urological diseases in a mammal comprising the steps of
i) determining the amount of a 5HT2a polynucleotide in a sample taken from said mammal, and
ii) determining the amount of 5HT2a polynucleotide in healthy and/or diseased mammals.
19 - 20 . (canceled)
21 . A pharmaceutical composition for the treatment of a disease selected from the group consisting of cardiovascular diseases, respiratory diseases, dermatological diseases, gastroenterological diseases, cancer, inflammation, metabolic diseases, hematological diseases, muscle skeleton diseases, neurological diseases and urological diseases in a mammal, comprising a therapeutic agent which regulates the activity of a 5HT2a polypeptide, wherein said therapeutic agent is
i) a small molecule,
ii) an RNA molecule,
iii) an antisense oligonucleotide,
iv) a polypeptide,
v) an antibody, or
vi) a ribozyme.
22 . A pharmaceutical composition for the treatment of a disease selected from the group consisting of cardiovascular diseases, respiratory diseases, dermatological diseases, gastroenterological diseases, cancer, inflammation, metabolic diseases, hematological diseases, muscle skeleton diseases, neurological diseases, and urological diseases in a mammal, comprising a 5HT2a polynucleotide.
23 . A pharmaceutical composition for the treatment of a disease selected from the group consisting of cardiovascular diseases, respiratory diseases, dermatological diseases, gastroenterological diseases, cancer, inflammation, metabolic diseases, hematological diseases, muscle skeleton diseases, neurological diseases, and urological diseases in a mammal, comprising a 5HT2a polypeptide.
24 - 26 . (canceled)