Compositions which regulate the epithelial brush border Na
A synthetic peptide modeled on the IRCX binding area of NHE3, is a competitive inhibitor of the IRCX and both stimulates basal NHE3 activity and prevents elevated Ca 2+ and cAMP inhibition of NHE3. Methods of its preparation and use in the prevention and/or treatment of gastrointestinal disease, such as diarrhea are provided.
1. A sodium/hydrogen Exchanger 3 (NHE3) Inhibitory Regulatory Complex ICRX Competing Peptide (ICRX-CP), or a functional portion or analog or derivative thereof.
2. A peptide comprising the amino acid sequence of SEQ ID NO: 1, or a functional portion or analog or derivative thereof.
3. The peptide of claim 1 , wherein the peptide binds NHE3 IRCX binding domain or functional portion or fragment thereof.
4. The peptide of claim 3 , wherein the NHE3 IRCX binding domain comprises amino acids 568-605 of the NHE3 protein, or a functional portion or fragment thereof.
5. The peptide of claim 1 , wherein the peptide stimulates basal NHE3 activity and prevents elevated Ca 2+ and cAMP inhibition of NHE3.
6. A pharmaceutical composition comprising the peptide of claim 1 , and a pharmaceutically acceptable carrier.
7. The pharmaceutical composition of claim 6 , further comprising a second therapeutic agent.
8. The pharmaceutical composition of claim 6 , wherein the second therapeutic agent is selected from the group consisting of: anti-motility, antidiarrheals, antibiotics, antihelminths, and anti-parasiticals.
9. The pharmaceutical composition of claim 6 , further comprising an effective amount of a probiotic composition comprising one or more strains of probiotic microorganisms.
10. A method of treatment of a gastrointestinal disease in a mammal comprising administering to the mammal the peptide of claim 1 , or the pharmaceutical composition of claim 6 , in an effective amount to modulate or treat the gastrointestinal disease.
11. The method of claim 10 , wherein the gastrointestinal disease is selected from the group consisting of acute, prolonged, and chronic diarrhea.
12. The method of claim 11 , wherein the gastrointestinal disease is chronic diarrhea.
13. A method for prophylaxis of diarrhea in the gastrointestinal tract of a subject, the method comprising:
administering to the subject an effective amount of the peptide of claim 1 , or the pharmaceutical composition of claim 6 , to prevent and/or treat the symptoms of diarrhea in the subject.
14. The method of claim 13 , wherein the pharmaceutical composition further comprises a second therapeutic agent.
15. The method of claim 14 , wherein the second therapeutic agent is selected from the group consisting of: anti-motility, antidiarrheals, antibiotics, antihelminths, and anti-parasiticals.