CARBACHOL, BUT NOT NOREPINEPHRINE, NMDA, IONOMYCIN, OUABAIN, OR PHORBOL-MYRISTATE ACETATE, INCREASES INOSITOL 1,3,4,5-TETRAKISPHOSPHATE ACCUMULATION IN RAT-BRAIN CORTICAL SLICES

Ionomycin, a Ca2+ ionophore, stimulated phosphoinositide breakdown in rat brain cortical slices incubated in the presence of 1.2 mM Ca2+, bu t, unlike muscarinic cholinergic stimulation, it had little effect on inositol 1,3,4,5-tetrakisphosphate accumulation. However, at 2 min, th e increase in inositol 1,4,5-trisphosphate due to 10 mu M ionomycin wa s equivalent to that seen with 1 mM carbachol. Phorbol 12-myristate 13 -acetate or high K+ (30 mM) increased inositol 1,4,5-trisphosphate, bu t not inositol 1,3,4,5-tetrakisphosphate accumulation. The stimulation of inositol 1,4,5-trisphosphate accumulation due to ionomycin, unlike that seen with carbachol, was abolished in buffer containing 0.2 mM C a2+ The increase in inositol 1,3,4,5-tetrakisphosphate accumulation in brain slices due to 1 mM carbachol ranged from 55 to 68% of that for inositol 1,4,5-trisphosphate, Norepinephrine, NMDA, veratridine, and o uabain also increased inositol 1,4,5-trisphosphate, but had minimal ef fects on inositol 1,3,4,5-tetrakisphosphate accumulation. These result s suggest that there is something unique about the stimulation of inos itol 1,3,4,5-tetrakisphosphate accumulation by carbachol, which is als o the only one of these agents that is able to activate phosphoinositi dase C beta(1) in isolated rat brain membranes.