Treatment with dexamethasone down-regulates IgE-receptor-mediated signals and up-regulates adenosine-receptor-mediated signals in a rat mast cell (RBL-2H3) line.
As reported by other workers, the treatment of rat basophilic leukemia RBL-2H3 cells with dexamethasone resulted in a marked decrease in responsiveness to Ag-stimulation. All responses measured, which included hydrolysis of inositol phospholipids, increase in concentration of cytosolic Ca2+, release of arachidonic acid and the secretion of serotonin, were suppressed, but once the cells were permeabilized the inhibitory actions of dexamethasone were no longer apparent. This suggested that all the necessary components of the stimulatory cascade were intact in the dexamethasone-treated cells. The measurement of phospholipase C activity in cell extracts and studies with phorbol ester also indicated that the cells contained a normal complement of phospholipase C and protein kinase C activity. We had previously shown that both Ag and the adenosine analog, 5'-(N-ethylcarboxamide)-adenosine, can activate phospholipase C, but they do so through different G proteins. Interestingly, the activation of phospholipase C by 5'-(N-ethylcarboxamide)-adenosine and the ensuing stimulatory events were markedly enhanced in dexamethasone-treated cells. The treatment with dexamethasone thus did not result in direct suppression of effector systems, but instead resulted in the selective modulation of the coupling between receptors and the effector systems by mechanisms that require soluble cytosolic factors.
Collado-Escobar
D
D
Laboratory of Chemical Pharmacology, National Heart Lung and Blood Institute, Bethesda, MD 20892.
Cunha-Melo
J R
JR
Beaven
M A
MA
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D008407:Mast Cells / Q000502:physiology*; D051381:Rats; D011961:Receptors, Fc / Q000378:metabolism*; D017455:Receptors, IgE; D011983:Receptors, Purinergic / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology; D015854:Up-Regulation
D000944:Antigens, Differentiation, B-Lymphocyte; D001095:Arachidonic Acids; D007295:Inositol Phosphates; D011961:Receptors, Fc; D017455:Receptors, IgE; D011983:Receptors, Purinergic; D013873:Thionucleotides; D016718:Arachidonic Acid; D012701:Serotonin; D019830:Adenosine-5'-(N-ethylcarboxamide); D016244:Guanosine 5'-O-(3-Thiotriphosphate); D003907:Dexamethasone; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D000241:Adenosine; D002118:Calcium