Methods and Compositions For P2X Receptor Calcium Entry Channels and Other Calcium Entry Mechanisms

Abstract

This invention relates generally to a method of increasing cytosolic Ca 2+ levels in mammalian cells comprising contacting P2X receptor Ca 2+ entry channels or any and all other Ca 2+ entry channels or mechanisms on the cell with an effective amount of a small molecule, and a composition comprising the small molecule in a delivery system. The invention has broad applicability in the pharmaceutical industry as a method of treating airway diseases (such as cystic fibrosis and asthma), ailments of the lung and airways (such as those caused by common cold pathogens or allergens in allergy), kidney diseases and renal hypertensive disorders (such as polycystic kidney disease and salt-sensitive hypertension syndromes), and endocrine disorders (such as diabetes).

1 - 36 . (canceled) 
   
   
       37 . A composition comprising zinc and a saline solution, wherein the saline solution has low Na+, is enriched with Ca 2+ , and is modified to an alkaline pH. 
   
   
       38 . A nasal spray, nebulizer, or aerosol inhaler comprising the composition of  claim 37 . 
   
   
       39 - 40 . (canceled) 
   
   
       41 . The composition of  claim 37 , wherein the zinc is not in the form of zincum gluconium. 
   
   
       42 . A method of treating a bacterial infection in a subject, comprising administering to the subject the composition of  claim 37 . 
   
   
       43 . A method of reducing inflammation in a subject, comprising administering to the subject the composition of  claim 37 . 
   
   
       44 . A method of treating polycystic kidney disease in a subject, comprising administering to the subject the composition of  claim 37 . 
   
   
       45 . A method of treating a subject with an endocrine disorder, comprising administering to the subject the composition of  claim 37 . 
   
   
       46 - 47 . (canceled) 
   
   
       48 . A method of screening for an airway epithelial Ca 2+  entry channel agonist, comprising
 (a) contacting an airway epithelial cell with a test compound;   (b) detecting calcium levels in the airway epithelial cell; and   (c) screening for a sustained elevation in calcium as compared to a control level, indicating an airway epithelial Ca 2+  entry channel agonist.   
   
   
       49 . The method of  claim 48 , wherein the Ca 2+  entry channel is selected from the group consisting of a P2X purinergic receptor Ca 2+  entry channel, a transient receptor potential (TRP) Ca 2+  entry channel, a store-operated Ca 2+  (SOC) entry channel, a calcium release activated channel (ICRAC), and a CAT-1 Ca 2+  entry channel. 
   
   
       50 . The method of  claim 48  further comprising the step of:
 (d) screening for reversibility of response by removing the agonist during the assay.   
   
   
       51 . The method of  claim 50 , further comprising the step of:
 (e) screening for dependence upon extracellular Ca 2+  by repeating the assay in a solution devoid of extracellular Ca 2+ .   
   
   
       52 . The method of  claim 48 , wherein the airway epithelial cell is a cystic fibrosis airway epithelial cell. 
   
   
       53 - 57 . (canceled) 
   
   
       58 . The method of  claim 48 , wherein the airway epithelial cell is in a solution containing an effective amount of ATP. 
   
   
       59 - 60 . (canceled) 
   
   
       61 . The method of  claim 48 , wherein the airway epithelial cell is in a solution containing an effective amount of zinc. 
   
   
       62 - 63 . (canceled) 
   
   
       64 . The method of  claim 48 , wherein the airway epithelial cell is in an alkaline solution. 
   
   
       65 - 145 . (canceled)