Effect of hydrocortisone and disodium cromoglycate on mast cell-mediator release induced by substance P.
Release of inflammatory mediators from mast cells following immunoglobulin bridging by specific allergens triggers episodes of asthma and bronchial hyperreactivity. Recent evidence has shown that neuropeptides, such as substance P (SP), may modulate the pulmonary inflammatory response in these airway diseases. This suggests that SP may affect secretory events of mast cells. To investigate these effects, resident peritoneal mast cells were collected from Sprague-Dawley male rats and stimulated with Con A (utilizes surface-bound immunoglobulin), compound 48/80 (acts in a peptide-like manner) and SP. Secretion was assessed as the release of preloaded [14C]serotonin. All secretagogues induced dose-dependent release. Pharmacologic modulation of release was then studied with two drugs employed for treatment of airway disease, hydrocortisone, a classical anti-inflammatory steroid, and disodium cromoglycate (DSCG). Following pretreatment with 5 mumol/l hydrocortisone, serotonin release induced by Con A was inhibited by 59%. No inhibition was noted with compound 48/80 or SP release. Similarly, following DSCG (300 mumol/l) pretreatment, 40% inhibition of release was noted with Con A, but no inhibition occurred following compound 48/80- or SP-stimulated release. Collectively, these results suggest that mast cells possess multiple activation-secretion coupling pathways which respond differently to clinically used pharmacologic agents. Diseases involving SP modulation of mast cell mediator release may not be successfully treated with anti-inflammatory steroids or DSCG.
Heiman
A S
AS
College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee 32307, USA.
Newton
L
L
D000470:Alkaloids / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D003208:Concanavalin A / Q000276:immunology; D004205:Cromolyn Sodium / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine; D013373:Substance P / Q000276:immunology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000470:Alkaloids; D003208:Concanavalin A; D012701:Serotonin; D013373:Substance P; D003189:p-Methoxy-N-methylphenethylamine; D011493:Protein Kinase C; D019311:Staurosporine; D004205:Cromolyn Sodium; D006854:Hydrocortisone