Regulation of ins(3456)p4 signalling by a reversible kinase phosphatase and methods and compositions related thereto

• US 20060035810A1
• Filed: 03/18/2003
• Published: 02/16/2006
• Est. Priority Date: 03/18/2002
• Status: Abandoned Application

• Current Assignee: Human Services National Institutes of Health, University of Bath
• Original Assignee: University of Bath
• Inventors: Shears, Stephen B, Potter, Barry V.L, Riley, Andrew M
• Application Number:
  US10/508,363
• Publication Number:
  US 20060035810A1
• Time in Patent Office: Days
• US Class Current: 514/1
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C12N 9/16 acting on ester bonds (3.1)

Abstract

Provided is a method of increasing 3,4,5,6-tetrakisphosphate by increasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase, and a method of decreasing 3,4,5,6-tetrakisphosphate by decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase. A method of reducing salt, fluid or mucous secretion in a subject, comprising increasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in the subject is provided. A method of treating a disease that is exacerbated by salt, fluid or mucous secretion is also provided, comprising increasing the activity of inositol 1,3,4,5,6 pentakisphosphate phosphatase in a subject having a disease that is exacerbated by mucous, whereby mucous secretion is reduced and the disease is treated. Also provided is method of increasing salt and fluid secretion in a subject, comprising decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in the subject. A method of treating a disease that is treated by increased salt and fluid secretion is provided, comprising decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in a subject having a disease that is treated by increased salt and fluid secretion, whereby salt and fluid secretion is increased and the disease is treated.

Claims

1. A method of reducing salt, fluid or mucous secretion in a subject, comprising increasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in the subject.

3. The method of claim 1 wherein the step of increasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase comprises over-expressing inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase.

4. The method of claim 1 wherein the step of increasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase comprises adiministering to the subject a compound that activates inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase.

2. A method of treating a disease that is exacerbated by salt, fluid or mucous secretion, comprising increasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in a subject having a disease that is exacerbated by mucous, whereby salt, fluid or mucous secretion is reduced and the disease is treated.

5. The method of claim 2, wherein the disease is selected from the group consisting of asthma, bronchitis and the common cold.

6. A method of increasing salt and fluid secretion in a subject, comprising decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in the subject.

8. The method of claim 6 wherein the step of decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase comprises reducing the expression of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase.

9. The method of claim 6 wherein the step of decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase comprises administering to the subject a compound that decreases the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase.

7. A method of treating a disease that is treated by increased salt and fluid secretion, comprising decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in a subject having a disease that is treated by increased salt and fluid secretion, whereby salt and fluid secretion is increased and the disease is treated.

10. The method of claim 7, wherein the disease is cystic fibrosis.

11. A method of decreasing chloride secretion from calcium-activated chloride channels in a cell, comprising decreasing inositol 3,4,5,6 phosphate kinase activity in the cell.

13. The method of claim 11, wherein the cell is selected from the group consisting of an epithelial cell, a neuron and a smooth muscle cell.

12. A method of decreasing chloride secretion from calcium-activated chloride channels in a cell, comprising increasing inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase activity in the cell.

14. A method of increasing chloride secretion from calcium-activated chloride channels in a cell, comprising increasing inositol 3,4,5,6 phosphate kinase activity in the cell.

16. The method of claim 14, wherein the cell is selected from the group consisting of an epithelial cell, a neuron and a smooth muscle cell.

15. A method of increasing the activity of calcium-activated chloride channels in a cell, comprising decreasing inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase activity in the cell.

17. A method of reducing inositol 3,4,5,6 tetrakisphosphate 1-phosphate-mediated inhibition of insulin release, comprising decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in the subject.

18. A method of treating a disease that is exacerbated by inhibition of insulin secretion, comprising decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in a subject having a disease that is exacerbated by inhibition of insulin secretion, whereby the inhibition of insulin secretion is reduced and the disease is treated.

19. The method of claim 18 wherein the disease is type 2 diabetes.

20. The method of claim 18 wherein the step of decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase comprises reducing expression of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase.

21. The method of claim 18 wherein the step of decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase comprises administering to the subject a compound that inhibits inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase.

22. A method of increasing inositol 3,4,5,6 tetrakisphosphate 1-phosphate-mediated inhibition of insulin release, comprising increasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in the subject.

23. A method of treating a disease that is treated by increasing levels of inositol 3,4,5,6 tetrakisphosphate thereby modulating inositol 3,4,5,6 tetrakisphosphate 1-phosphate-regulated chloride channels in intracellular vesicles, comprising decreasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in a subject having a disease that is treated by decreased inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase activity, whereby the disease is treated.

25. The method of claim 23 wherein the step of modulating the activity of inositol 3,4,5,6 tetrakisphosphate 1-phosphate-regulated channels comprises altering the expression of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase.

26. The method of claim 23 wherein the step of modulating the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase comprises administering to the subject a compound that decreases the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase.

24. A method of treating a disease that is treated by decreasing levels of inositol 3,4,5,6 tetrakisphosphate thereby modulating inositol 3,4,5,6 tetrakisphosphate 1-phosphate-regulated chloride channels in intracellular vesicles, comprising increasing the activity of inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase in a subject having a disease that is treated by increased inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase activity, whereby the disease is treated.

27. A method of decreasing chloride secretion from calcium-activated chloride channels in an intracellular vesicle, comprising decreasing inositol 3,4,5,6 phosphate kinase activity in the cell.

28. A method of increasing chloride secretion from calcium-activated chloride channels in an intracellular vesicle, comprising increasing inositol 3,4,5,6 phosphate kinase activity in the intracellular vesicle.

29. A method of increasing the activity of calcium-activated chloride channels in an intracellular vesicle, comprising decreasing inositol 1,3,4,5,6 pentakisphosphate 1-phosphatase activity in the intracellular vesicle.