Inhibition of amylin release

Abstract

A method of determining the ability of a compound to both bind to somatostatin type-5 receptor (“SSTR-5”) and inhibit amylin release. The method includes obtaining a preparation, either a cell preparation or a membrane preparation, which contains SSTR-5; incubating the preparation, the compound, and a SSTR-5 ligand, at least one of the ligand and the compound being detectably labeled; determining the ability of the compound to compete against the ligand for binding to SSTR-5; if and only if the compound is determined to be able to bind to SSTR-5, obtaining pancreatic cells; incubating the compound, the pancreatic cells, and an amylin release stimulator under conditions in which the amylin release stimulator would induce release of amylin from the pancreatic cells; and determining the ability of the compound to inhibit amylin release. Also disclosed is a method of treating hyperamylinemia with a ligand selective for SSTR-5.

What is claimed is:  
     
         1 . A method of determining the ability of a compound to both bind to somatostatin type-5 receptor and inhibit amylin release from amylin-secreting pancreas cells, said method comprising: 
 obtaining a preparation which contains somatostatin type-5 receptor;    incubating said preparation, said compound, and a somatostatin type-5 receptor ligand, at least one of said ligand and said compound being detectably labeled;    determining the ability of said compound to compete against said ligand for binding to somatostatin type-5 receptor;    if and only if said compound is determined to be able to bind to somatostatin type-5 receptor, obtaining amylin-secreting pancreatic cells;    incubating said compound, said pancreatic cells, and an amylin release stimulator under conditions in which said amylin release stimulator would induce release of amylin from said pancreatic cells; and    determining the ability of said compound to inhibit amylin release.    
     
     
         2 . A method of  claim 1 , wherein said preparation is a cell preparation.  
     
     
         3 . A method of  claim 1 , wherein said preparation is a membrane preparation.  
     
     
         4 . A method of  claim 1 , wherein said preparation is derived from a rodent olfactory bulb.  
     
     
         5 . A method of  claim 1 , wherein said preparation is derived from CHO-K1 cells transfected with the human somatostatin type-5 receptor.  
     
     
         6 . A method of  claim 3 , wherein said preparation is derived from a rodent olfactory bulb.  
     
     
         7 . A method of  claim 3 , wherein said preparation is derived from CHO-K1 cells transfected with the human somatostatin type-5 receptor.  
     
     
         8 . A method of  claim 1 , wherein said ligand is detectably labeled.  
     
     
         9 . A method of  claim 3 , wherein said ligand is detectably labeled.  
     
     
         10 . A method of  claim 1 , wherein said pancreatic cells are pancreatic islet cells.  
     
     
         11 . A method of  claim 10 , wherein said pancreatic islet cells are β cells.  
     
     
         12 . A method of  claim 1 , wherein said pancreatic cells are amylinoma cells.  
     
     
         13 . A method of  claim 1 , wherein said pancreatic cells are cells in an isolated rodent pancreas.  
     
     
         14 . A method of  claim 1 , wherein said pancreatic cells are RINm5f cells.  
     
     
         15 . A method of  claim 3 , wherein said pancreatic cells are pancreatic islet cells.  
     
     
         16 . A method of  claim 15 , wherein said pancreatic islet cells are β cells.  
     
     
         17 . A method of  claim 3 , wherein said pancreatic cells are amylinoma cells.  
     
     
         18 . A method of  claim 3 , wherein said pancreatic cells are cells in an isolated rodent pancreas.  
     
     
         19 . A method of  claim 3 , wherein said pancreatic cells are RINm5f cells.  
     
     
         20 . A method of treating hyperamylinemia in a subject, said method comprising administering to said subject an amount of a somatostatin type-5 receptor agonist, said amount being effective in treating hyperamylinemia.  
     
     
         21 . A method of  claim 20 , wherein said somatostatin type-5 agonist is at least 3 times as selective for somatostatin type-5 receptor as for somatostatin type-2 receptor.  
     
     
         22 . A method of  claim 21 , wherein said somatostatin type-5 agonist is at least 10 times as selective for somatostatin type-5 receptor as for somatostatin type-2 receptor.