Influence of glucocorticoids on histamine release and 45calcium uptake by isolated rat mast cells.
Hydrocortisone and prednisolone inhibited the histamine release from isolated rat mast cells induced by antigen, the ionophore A23187, and compound 48/80 in the absence and in the presence of calcium. Hydrocortisone reduced the response to the different releasing agents by 50% in the concentration range 2-6 X 10(-4) M, whereas prednisolone was about 1.5 times more potent. The inhibitory effect of hydrocortisone had a rapid onset of action and maximal inhibition was observed after preincubation for 20 minutes. The effect of hydrocortisone was reversed by including 2 mM glucose in the medium. The reversal was only partial with antigen and the ionophore A23187, indicating a greater energy requirement of these releasing agents compared with compound 48/80. The inhibition of the histamine release was accompanied by a concentration-related inhibition of the 45Ca uptake, except with the ionophore. The inhibition of the 45Ca uptake was also reversed by glucose, but differences were noted concerning the influence of preincubation time. The observations are explained by an association of 45Ca to cellular material, e.g. granules, secondary to the release process. The effects of hydrocortisone and prednisolone were qualitatively identical and were not observed with estriol. The glucocorticoid inhibition of histamine release does not seem to be caused by effects on phospholipase activity or cyclic AMP metabolism. The present observations are fully consistent with an impaired mitochondrial function as the mechanism for the mast cell effects of the glucocorticoids.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D005938:Glucocorticoids / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D002132:Calcium Radioisotopes; D005938:Glucocorticoids; D000001:Calcimycin; D003189:p-Methoxy-N-methylphenethylamine; D005947:Glucose; D002118:Calcium; D006854:Hydrocortisone