Inhibition of amylin release

• US 5,763,200 A
• Filed: 05/12/1995
• Issued: 06/09/1998
• Est. Priority Date: 05/12/1995
• Status: Expired due to Fees

• Current Assignee: Ipsen Pharma Sas (Ipsen Sa)
• Original Assignee: Biomeasure, Inc. (Ipsen Sa)
• Inventors: Cawthorne, Michael Anthony, Davenport, Michelle, Dunmore, Simon Jon
• Primary Examiner(s): Hutzell, Paula K.
• Assistant Examiner(s): HAYES, ROBERT CLINTON
• Application Number:
  US08/440,061
• Time in Patent Office: 1,124 Days
• Field of Search: 435/7.1, 435/7.2, 435/7.21, 435/240.2, 435/69.1, 435/7.23, 435/361
• US Class Current: 435/7.21
• CPC Class Codes: A61K 38/31 Somatostatins
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/02 of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
• CPC Class Codes: G01N 2333/655 Somatostatins
• CPC Class Codes: G01N 2333/72 for hormones
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

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 hyper-amylinemia with a ligand selective for SSTR-5.

Claims

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 CHO-K1 cells transfected with DNA encoding the human somatostatin type-5 receptor or a membrane preparation obtained therefrom;

incubating said CHO-K1 cells or a membrane preparation obtained therefrom, 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 binds 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 ligand is detectably labeled.

3. A method of claim 1, wherein said amylin-secreting pancreatic cells are pancreatic islet cells.

4. A method of claim 3, wherein said pancreatic islet cells are β

cells.

5. A method of claim 1, wherein said pancreatic cells are cells in an isolated rodent pancreas.