ABSTRACT
Corticosteroids enhance beta-adrenergic responses by actions at both beta-adrenoceptor (beta-AR) and post-beta-AR sites. The present study investigated the effects of dexamethasone on beta-AR density, high-affinity beta-agonist binding, G(s)alpha and G(i)alpha protein expression, and cAMP responses in bovine tracheal smooth muscle (bTSM). Dexamethasone treatment of cultured bTSM cells increased total beta-AR density 1.6- to 1.9-fold as assessed by the saturation binding of [(3)H]CGP-12177 and by displacement of radioligand binding with isoproterenol. Isoproterenol bound to the beta-AR at two sites, a high-affinity site with a density of 5.9 +/- 1.2 fmol/mg protein and a low-affinity site with a density of 16.9 +/- 1. 0 fmol/mg protein. Dexamethasone increased both high- and low-affinity isoproterenol binding sites to 11.1 +/- 2.2 and 25.9 +/- 2.1 fmol/mg protein, respectively, without influencing agonist binding affinities. Dexamethasone also selectively increased G(s)alpha protein levels from 0.99 +/- 0.14 to 1.46 +/- 0.17 microg/mg protein without affecting G(i)alpha levels. The net effect of these changes was a 1.8-fold increase in maximal isoproterenol-induced cAMP generation in dexamethasone-treated bTSM cells. These findings provide new insights into the corticosteroid regulation of beta-adrenergic signaling pathways in airway smooth muscle.
Subject(s)
Adrenergic beta-Agonists/pharmacology , Dexamethasone/pharmacology , GTP-Binding Protein alpha Subunits, Gs/metabolism , Glucocorticoids/pharmacology , Muscle, Smooth/cytology , Muscle, Smooth/metabolism , Propanolamines/pharmacology , Trachea/cytology , Animals , Blotting, Western , Cattle , GTP-Binding Protein alpha Subunits, Gs/analysis , Isoproterenol/pharmacology , Ligands , Membrane Proteins/analysis , Membrane Proteins/metabolism , Muscle, Smooth/drug effects , Radioligand Assay , Trachea/drug effects , Trachea/metabolism , TritiumABSTRACT
Myelopathy is an infrequently reported complication of bacterial meningitis. We report the case of a preterm neonate with group B streptococcal meningitis who developed acute transverse myelopathy with subsequent spinal cord cavitation noted by MRI. The destruction of the cerebellum and obstructive hydrocephalus resulted in a posterior fossa cyst.