Specificity and inhibition of glucocorticoid-induced macrocortin secretion from rat peritoneal macrophages

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Abstract
1 The secretion of the phospholipase A2-inhibitor macrocortin and the binding of dexamethasone were studied in suspensions of rat peritoneal macrophages. 2 Corticosteroid-induced macrocortin secretion was specific for glucocorticoids and did not occur in response to glucocorticoid antagonists or other steroids or in response to non-steroid macrophage activators (formyl-methionyl-leucyl-phenylalanine f-MLP), the calcium ionophore A23187, phorbol myristate acetate (PMA) and lipopolysaccharide-E.-coli(LPS)). 3 The apparent potency of competition by secretory glucocorticoids for dexamethasone binding to the macrophage parallelled their ability to induce secretion, implying that these binding sites represent the receptors by which macrocortin secretion is initiated. 4 Agents which interfere with microtubule assembly (colchicine, vinblastine and trimethylcol-chicinic acid) and prostacyclin and dibutyryl cyclic AMP inhibit macrocortin secretion. 5 Inhibition studies of glucocorticoid-induced macrocortin secretion also suggest dependence upon metabolic energy, a source of Ca2+ and proteolysis and glycosylation prior to secretion.