Angiotensin II priming of aldosterone secretion with agents that enhance Ca2+ influx

We have previously shown that angiotensin II (AngII) is able to prime, or s ensitize, the secretory response of cultured bovine adrenal glomerulosa cel ls to the Ca2+ channel agonist, BAY K8644. We examined the ability of AngII to prime glomerulosa cells to an elevated extracellular K+ level, a physio logical agonist that also triggers Ca2+ influx. K+ (9 mM) elicited enhanced secretion in AngII-primed cells compared to those with no prior exposure t o the hormone, suggesting that AngII can sensitize glomerulosa cells to res pond to increases in extracellular K+. The potential involvement of protein kinase C (PKC) in priming was investigated by determining whether enhanced Ca2+ influx could maintain the AngII-induced phosphorylation of the endoge nous PKC substrate, myristoylated, alanine-rich C kinase substrate (MARCKS) . Incubation with the AngII antagonist, saralasin, for 30 min following an AngII exposure reduced the AngII-induced increase in MARCKS phosphorylation . 100 nM BAY K8644 together with saralasin was unable to maintain AngII-sti mulated MARCKS phosphorylation. On the other hand, phosphorylation of the s teroidogenic acute regulatory (StAR) protein was sustained with saralasin e xposure, both in the presence and absence of BAY K8644. This observation su ggests that persistent StAR phosphorylation/activation may play a role in p riming. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.