Experimental intestinal hypersensitivity. Effect of four anti-allergic drugs on protein uptake, permeability to sugars and mucosal mast-cell activation.
The ability of four drugs with anti-allergic action to modulate the uptake of bystander protein, lactulose/rhamnose permeability ratios and mast cell activation was studied in rats presensitized with egg albumin in alum and challenged intraduodenally with the same antigen. Beclomethasone dipropionate (BDP) and nedocromil both significantly reduced the uptake of the bystander protein, bovine serum albumin (P < 0.002 and P > 0.02 respectively). BDP also significantly reduced sugar permeability (P < 0.01). In animals with elevated lactulose/rhamnose permeability ratios we confirmed our earlier observation of a significant correlation between levels of the specific mucosal mast cell protease Rat Chymase II (RChyII-previously known as RMCPII) and the sugar ratios. None of the drugs had any influence on the levels of mast cell protease II released following challenge and there was no correlation between the histological light microscopic appearance of the mast cells and the experimental treatment administered. Our results suggest that in the gut the pharmacological effect of anti-allergic drugs may be complex. Some, such as nedocromil, appear to act only on the mechanisms underlying increased protein uptake whereas others, such as BDP, appear to abrogate both increased protein uptake and increased sugar permeability.
Turner
M W
MW
Molecular Immunology Unit, Institute of Child Health, London, UK.
Boulton
P
P
Strobel
S
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001507:Beclomethasone / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects*; D053818:Chymases; D004205:Cromolyn Sodium / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006967:Hypersensitivity / Q000188:drug therapy* / Q000196:embryology* / Q000276:immunology; D007408:Intestinal Absorption / Q000187:drug effects; D007410:Intestinal Diseases / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007792:Lactulose / Q000493:pharmacokinetics*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology*; D017835:Nedocromil / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012210:Rhamnose / Q000493:pharmacokinetics*; D012697:Serine Endopeptidases / Q000097:blood / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*; D013892:Thioxanthenes / Q000494:pharmacology; D044004:Xanthones
D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D013892:Thioxanthenes; D044004:Xanthones; D017835:Nedocromil; D012710:Serum Albumin, Bovine; D007792:Lactulose; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D001507:Beclomethasone; D004205:Cromolyn Sodium; D012210:Rhamnose; C010134:doxantrazole