Modulation of Agonist-Induced Inositol Phosphate Metabolism by Cyclic Adenosine 3′,5′- Monophosphate in Adrenal Glomerulosa Cells

Publisher Website
Google Scholar
Abstract
Activation of the cAMP messenger system was found to cause specific changes in angiotensin-II (AII)-induced inositol phosphate production and metabolism in bovine adrenal glomerulosa cells. Pretreatment of [3H]inositol-labeled glomerulosa cells with 8-bromo-cAMP (8Br-cAMP) caused both short and long term changes in the inositol phosphate response to stimulation by AII. Exposure to 8Br-cAMP initially caused dose-dependent enhancement (ED50 = 0.7 .mu.M) of the stimulatory action of AII (50 nM; 10 min) on the formation of D-myo-inositol 1,4,5-triphosphate [Ins(1,4,5)P3] and it immediate metabolites. This effect of 8Br-cAMP was also observed in permeabilized [3H]inositol-labeled glomerulosa cells in which degradation of Ins(1,4,5)P3 was inhibited, consistent with increased activity of phospholipase-C. Continued exposure to 8Br-cAMP for 5-16 h caused selective enhancement of the AII induced increases in D-myo-inositol 1,3,4,6-tetrakisphosphate [Ins(1,3,4,6)P4] and myo-inositol 1,4,5,6-tetrakisphosphate. The long term effect of 8Br-cAMP on the 6-phosphorylated InsP4 isomers, but not the initial enhancement of Ins(1,4,5)P3 formation, was inhibited by cycloheximide. The characteristic biphasic kinetics of AII-induced Ins(1,4,5)P3 formation were also changed by prolonged treatment with 8Br-cAMP to a monophasic response in which Ins(1,4,5)P3 increased rapidly and remained elevated during AII stimulation. In permeabilized glomerulosa cells treated with 8Br-cAMP for 16 h, the conversion of D-myo-inositol 1,3,4-triphosphate [Ins(1,3,4)P3] to Ins[1,3,4,6)P4 was consistently increased, whereas dephosphorylation of Ins(1,4,5)P3 to D-myo-inositol 1,4-biphosphate and of D-myo-inositol 1,3,4,5-tetrakisphosphate to Ins(1,3,4)P3, was reduced. Thus, the increased production of higher inositol phosphates during AII stimulation of 8Br-cAMP-treated cells results in part from increased phosphorylation of Ins(1,3,4)P3 to Ins(1,3,4,6)P4, as well as decreased Ins(1,4,5)P3-5-phosphatase activity. These findings demonstrate that interactions between the cAMP and inositol phosphate signal generation pathways in the glomerulosa cell lead to enhanced production of higher inositol phosphates that could mediate long term changes in the function of agonist-stimulated adrenal cells.

This publication has 15 references indexed in Scilit: