A novel action of glucocorticosteroid in inhibition of leukotriene C4 production by rat basophilic leukemia cells: suppression of the elevation of cytosolic free Ca2+ induced by antigen.
Rat basophilic leukemia (RBL-2H3) cells serve as a model to examine the role of elevated internal Ca2+ concentration ([Ca2+]i), following antigen (DNP10BSA)-induced stimulation of leukotriene C4 (LTC4) formation. A novel action of hydrocortisone (HC), to reduce increased [Ca2+]i and consequently inhibit LTC4 formation is assessed. Half-maximal time for elevation of [Ca2+]i induced by antigen was less than 1 min, and maximal elevation of [Ca2+]i (3-fold increase) was reached within 2-3 min. This high [Ca2+]i level waned gradually by 27% during 20 min of incubation. For induction of LTC4 formation, however, there was a refractory period of about 2 min, and half-maximal elevation was at 11 min. Following pretreatment with HC, the antigen-stimulated increase in [Ca2+]i was stunted by 41% at 2-3 min and by 73% at 20 min. LTC4 formation was almost abolished. There was a lag period of at least 2 h to observe any inhibition in both parameters, and the maximal inhibition was about 4 h. Cycloheximide, and receptor antagonist to glucocorticosteroid (RU486) completely prevented the inhibitory effects of HC on elevated [Ca2+]i and LTC4 formation. Estradiol and aldosterone (each at 2.10(-6) M) were virtually inactive, while another glucocorticosteroid, dexamethasone (2.10(-7) M) markedly suppressed antigen induction in both parameters. It is proposed that the inhibitory effect of HC on the formation of LTC4 could be attributed mainly to its ability to reduce elevated [Ca2+]i.
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Department of Hormone Research, The Weizmann Institute of Science, Rehovot, Israel.
Weissman
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BA
Zor
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004140:Dinitrophenols / Q000494:pharmacology; D004336:Drug Antagonism; D006854:Hydrocortisone / Q000494:pharmacology*; D007942:Leukemia, Experimental / Q000378:metabolism*; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D013189:SRS-A / Q000096:biosynthesis*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004140:Dinitrophenols; D013189:SRS-A; C034638:dinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; D015735:Mifepristone; D002118:Calcium; D006854:Hydrocortisone