Glucocorticoids enhance histamine-evoked catecholamine secretion from bovine chromaffin cells.
The synthetic glucocorticoid dexamethasone enhanced histamine-evoked catecholamine secretion from cultured bovine chromaffin cells. Dexamethasone enhanced the effects of histamine on both adrenergic (epinephrine-rich) and noradrenergic (norepinephrine-rich) chromaffin cells but had a more dramatic effect on noradrenergic cells. Histamine-evoked secretion in noradrenergic cells appeared to become rapidly inactivated, whereas the rate of secretion in adrenergic cells was nearly constant for up to 2 h; dexamethasone treatment attenuated the inactivation seen in noradrenergic cells. The effect of dexamethasone appeared after a lag of several hours and was maximal by 24 h. The EC50 for dexamethasone was approximately 1 nM. The effect of dexamethasone was mimicked by the glucocorticoid agonist RU 28362 and was blocked by the antagonist RU 38486, indicating that the effects of these steroids were mediated by the glucocorticoid or type II corticosteroid receptor. Histamine-evoked catecholamine secretion in both dexamethasone-treated and untreated cells was blocked by the H1 histamine receptor antagonist mepyramine but was not affected by the H2 antagonist cimetidine; thus, dexamethasone appeared to enhance an H1 receptor-mediated process. In the absence of glucocorticoids, H1 receptor mRNA levels were higher in adrenergic than in noradrenergic cells. Dexamethasone increased H1 receptor mRNA levels in both cell types. The increased expression of H1 receptors presumably contributes to the enhancement of histamine-evoked catecholamine secretion by glucocorticoids. Glucocorticoids may play a physiological role in modulating the responsiveness of chromaffin cells to histamine and other stimuli.
Choi
A Y
AY
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637.
Fukui
H
H
Perlman
R L
RL
D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D002927:Cimetidine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011738:Pyrilamine / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011969:Receptors, Histamine H1 / Q000032:analysis / Q000235:genetics
D000732:Androstanols; D002395:Catecholamines; D005938:Glucocorticoids; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D003907:Dexamethasone; D002927:Cimetidine; D006632:Histamine; D011738:Pyrilamine