FK506 blocks intracellular Ca2+ oscillations in bovine adrenal glomerulosacells

The inositol 1,4,5-trisphosphate (InsP(3)) receptor is a ligand-gated Ca2channel playing an important role in the control of intracellular Ca2+. In the study presented here, we demonstrate that angiotensin (AngII), phorbol ester (PMA), and FK506 significantly increase the level of InsP(3) receptor phosphorylation in intact bovine adrenal glomerulosa cells. With a back-ph osphorylation approach, we showed that the InsP(3) receptor is a good subst rate for protein kinase C (PKC) and that FK506 increases the level of PKC-m ediated InsP(3) receptor phosphorylation. With a microsomal preparation fro m bovine adrenal cortex, we showed that PKC enhances the release of Ca2+ in duced by a submaximal dose of InsP(3). We also showed that FK506 blocks int racellular Ca2+ oscillations in isolated adrenal glomerulosa cells by progr essively increasing the intracellular Ca2+ concentration to a high plateau level. This effect is consistent with an inhibitory role of FK506 on calcin eurin dephosphorylation of the InsP(3) receptor, thus keeping the receptor in a phosphorylated, high-conductance state. Our results provide further ev idence for the crucial role of the InsP(3) receptor in the regulation of in tracellular Ca2+ oscillations and show that FK506, by maintaining the phosp horylated state of the InsP(3) receptor, causes important changes in the Ca 2+ oscillatory process.