Angiotensin II-stimulated changes in calcium metabolism in cultured glomerulosa cells

Studies were performed to evaluate the relationships between the effects of angiotensin II on calcium metabolism and cytosolic free calcium concentration in primary monolayer cultures of bovine adrenal glomerulosa cells. As noted previously (Kramer (1988) Am. J. Physiol. (in press], angiotensin II produced rapid dose-dependent increases in cytosolic calcium characterized by both an initial transient component and a secondary sustained component. In the absence of extracellular calcium, angiotensin II produced an initial increase in cytosolic calcium comparable to that produced in the presence of calcium, but failed to maintain a sustained calcium signal. The initial, angiotensin-stimulated increase in cytosolic calcium was inhibited by dantrolene and 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8) in a concentration-dependent fashion. The onset of the angiotensin-stimulated calcium signal was accompanied by a dose-dependent increase in the rate of calcium efflux that achieved a maximum within 2-3 min and then declined to a level 2.5-3 times that from control cells. The initial rate of calcium influx was also increased about 2.5-fold by angiotensin II, an effect that was only apparent in cells that had been treated with the peptide for at least 5 min. These results indicate that the calcium signal produced by angiotensin II is initiated by the rapid mobilization of calcium from an intracellular site(s) and sustained by the continued uptake of extracellular calcium. Moreover, the kinetics of the calcium signal as well as the final, sustained calcium concentration achieved reflect the balance between intracellular calcium release, calcium influx and calcium efflux.