Stimulus-secretion coupling in porcine adrenal chromaffin cells: Acute effects of glucocorticoids

Recent studies from this laboratory have established that long-term exposur e (48 hr) to glucocorticoids can modulate voltage-gated Ca2+ channel activi ty and subsequent intracellular Ca2+ transients in porcine adrenal medullar y chromaffin (PAMC) cells maintained in primary culture. Consistent with ma ny steroid hormone-mediated responses, this chronic effect of glucocorticoi ds probably involves increased gene expression and protein synthesis. Howev er, there is now considerable evidence to suggest that steroids can also el icit acute, non-genomic effects. The aim of the present study was to determ ine whether acute exposure to glucocorticoids also affects nicotinic recept or-dependent catecholamine (CAT) secretion and Ca2+ signaling in PAMC cells . Acute exposure to dexamethasone (DEX) dose-dependently attenuated the deg ree of nicotine (NIC)-induced CAT secretion, as well as the amplitude of NI C-induced intracellular Ca2+ transients. Significant inhibition of CAT secr etion occurred immediately upon addition of DEX, reached maximal levels wit hin 5 min of exposure to DEX, and was rapidly reversible after steroid wash out. The endogenous porcine glucocorticoid cortisol elicited similar effect s, In contrast, DEX had no significant effect on KCl-induced CAT secretion or intracellular Ca2+ transients. These data demonstrate that acute exposur e to glucocorticoids can modulate stimulus-secretion coupling in PAMC cells and suggest that the primary site of action is the nicotinic receptor. (C) 1999 Wiley-Liss, Inc.