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

Recent studies from this laboratory have established that long-term exposure (48 hr) to glucocorticoids can modulate voltage-gated Ca²⁺ channel activity and subsequent intracellular Ca²⁺ transients in porcine adrenal medullary chromaffin (PAMC) cells maintained in primary culture. Consistent with many steroid hormone-mediated responses, this chronic effect of glucocorticoids probably involves increased gene expression and protein synthesis. However, there is now considerable evidence to suggest that steroids can also elicit acute, non-genomic effects. The aim of the present study was to determine whether acute exposure to glucocorticoids also affects nicotinic receptor-dependent catecholamine (CAT) secretion and Ca²⁺ signaling in PAMC cells. Acute exposure to dexamethasone (DEX) dose- dependently attenuated the degree of nicotine (NIC)-induced CAT secretion, as well as the amplitude of NIC-induced intracellular Ca²⁺ transients. Significant inhibition of CAT secretion occurred immediately upon addition of DEX, reached maximal levels within 5 min of exposure to DEX, and was rapidly reversible after steroid washout. The endogenous porcine glucocorticoid cortisol elicited similar effects. In contrast, DEX had no significant effect on KCl-induced CAT secretion or intracellular Ca²⁺ transients. These data demonstrate that acute exposure to glucocorticoids can modulate stimulus- secretion coupling in PAMC cells and suggest that the primary site of action is the nicotinic receptor.