Short term memory in the calcium messenger system. Evidence for a sustained activation of protein kinase C in adrenal glomerulosa cells

If adrenal glomerulosa cells are treated with angiotensin II for a period of 20-30 min, their subsequent response to either a rechallenge with the same concentration of angiotensin II or treatment with BAY K 8644, a calcium channel agonist, differs from the responses of control cells. Perifusion of control cells with 10 nM-angiotensin II leads to an increase in aldosterone secretory rate from 44 ± 7 to 166 ± 9 pg/min per 10⁶ cells, but perifusion of cells pretreated for a 20 min period with angiotensin II leads to an increase in secretory rate from 51 ± 9 to 209 ± 18 pg/min per 10⁶ cells. Likewise, treatment of control cells with 10 nM-BAY K 8644 leads to no significant increase in aldosterone secretory rate, but treatment of previously exposed cells to angiotensin II leads to an increase in rate from 51 ± 9 to 130 ± 11 pg/min per 10⁶ cells. This memory effect is time-dependent in two ways: (a) cells must be exposed to angiotensin II for 20 min or more before it is apparent; (b) the longer the time between removal of angiotensin II and the rechallenge, the less effect these agents have on aldosterone secretory rate. When cells are exposed to angiotensin II for 20 min and then treated with [Sar¹,Ala⁸]angiotensin II, a competitive antagonist of angiotensin II action, the aldosterone secretory rate falls to basal with a half time of 5-7 min. If BAY K 8644 is added simultaneously with [Sar¹,Ala⁸]angiotensin II, the secretory rate falls with a half-time of 35-60 min. BAY K 8644 increases Ca²⁺ influx rate to the same extent in the presence or absence of [Sar¹,Ala⁸]angiotensin II, and does not alter the effect of either angiotensin II or [Sar¹,Ala⁸]angiotensin II on the production of inositol tris-, bis-, or mono-phosphate. In cells treated with 10 nM-angiotensin II for either 20, 30 or 45 min, the extent of phosphorylation of four cellular proteins is increased. If cells treated for 20 min with angiotensin II are then treated with [Sar¹,Ala⁸]angiotensin II, and examined 15 min later (35 min), there is no longer an increase in the extent of phosphorylation of any of the four proteins. If such cells are then treated with 10 nM-BAY K 8644 and re-examined 5 min later (40 min), all four proteins show an increase in the extent of phosphorylation. Treatment of control cells with 10 nM-BAY K 8644 does not alter the extent of phosphorylation of any cellular proteins. These data indicate that inhibition of angiotensin II action leads to a rapid decrease in calcium influx rate, but a slower rate of relaxation of the C-kinase from its Ca²⁺-sensitive form back to its Ca²⁺-insensitive form.