Corticosteroids attenuate sensitization-induced membrane changes in airway smooth muscle cells.
Serum from immunized guinea pigs or highly purified IgG1 induces specific changes in electrical and contractile characteristics of airway smooth muscle (ASM) cells. In this study, the effect of hydrocortisone and prednisolone pre-treatment on the events caused by a passive in vitro sensitization of ASM cells was investigated. ASM preparations isolated from male guinea pigs were exposed to immunized serum (1:10 dilution) together with different concentrations of hydrocortisone or prednisolone administered simultaneously or 30, 120 or 240 min before addition of immunized serum. During sensitization as well as during consecutive specific antigen challenges (1 mg/ml ovalbumin), both the resting membrane potential (Em) and isometric force developed by airway smooth muscle preparations were determined. Em was determined with glass microelectrodes and isometric force was simultaneously measured with a copper-berylium strain gauge. Pretreatment with both hydrocortisone and prednisolone (in the range of 10(-8)-10(-4) M) attenuated sensitization-induced transient depolarization and steady state hyperpolarization of ASM cells and decreased the sensitization-induced development of the isometric force. Furthermore, pretreatment with either steroid significantly attenuated electrical and contractile responses to a specific antigen challenge. Inhibition of the events observed during sensitization occurred at steroid concentrations as low as 10(-8) M. We have also found that the duration of exposure of ASM cells to either of the tested steroids is critical in determining the magnitude of this inhibitory effect and seems to be more important than concentration of tested steroids.(ABSTRACT TRUNCATED AT 250 WORDS)
Souhrada
M
M
John B. Pierce Foundation Laboratory, New Haven, CT 06519.
Souhrada
J F
JF
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000276:immunology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D012137:Respiratory System / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D000305:Adrenal Cortex Hormones