Modifying the permeability of physiological barriers

Abstract

The degree of phosphorylation of serine and threonine residues of p100/p120 can affect the permeability of physiological barriers and also cell-cell adhesion properties. By changing physiological levels, various disorders can be treated, including multiple sclerosis, cancer, head injuries, oedema, stroke, inflammation and gastric ulcers. Furthermore, drugs can be allowed to pass across physiological barriers and the barriers can then be closed.

1 . A pharmaceutical composition comprising a drug and an agent capable of inducing the dephosphorylation of phosphorylated serine and/or threonine residue of p100 and/or p120, wherein the ability of the drug to cross a physiological barrier is improved.  
     
     
         2 . A combined preparation comprising a drug and an agent capable of inducing the dephosphorylation of phosphorylated serine and/or threonine residue of p100 and/or p120, for simultaneous, separate or sequential use in administering the drug across a physiological barrier.  
     
     
         3 . A nasal delivery system comprising 
 (a) an agent capable of inducing the dephosphorylation of phosphorylated serine and/or threonine residue of p100 and/or p120;    (b) a drug and an agent capable of inducing the dephosphorylation of phosphorylated serine and/or threonine residue of p100 and/or p120, wherein the ability of the drug to cross a physiological barrier is improved; or,    (c) a drug and an agent capable of inducing the dephosphorylation of phosphorylated serine and/or threonine residue of p100 and/or p120, for simultaneous, separate or sequential use in administering the drug across a physiological barrier.    
     
     
         4 . A method of screening comprising contacting a substance with p100 and/or p120 to determine whether the substance is capable of (a) inducing the phosphorylation or serine and/or threonine residues present in p100 and/or p120 or (b) inducing the dephosphorylation of phosphorylated serine and/or threonine residues present in p100 and/or p120.  
     
     
         5 . A method for screening comprising contacting protein kinase C with a substance to determine if the substance (a) is capable of inducing the phosphorylation of serine and/or threonine residues present in p100 and/or p120 or (b) is capable of inducing the dephosphorylation of phosphorylated serine and/or threonine residues present in p100 and/or p120, wherein said screen is used to identify inhibitors or activators of protein kinase C.