Manganese Stimulates the Incorporation of [3H]Inositol into a Pool of Phosphatidylinositol in Brain That Is Not Coupled to Agonist‐Induced Hydrolysis

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Abstract
Mn2+ greatly increases the incorporation of myo‐[3H]inositol into phosphatidylinositol (PI) of brain and other tissues by stimulating the activity of a PI‐myoinositol exchange enzyme. This study examined the ability of norepinephrine (NE) and carbachol to stimulate the hydrolysis of [3H]PI formed in the absence and presence of Mn2+‐stimulated [3H]inositol exchange. Rat cerebral cortical slices were incubated with myo‐[3H]inositol for 60 min in an N‐2‐hydroxyethyl piperazine‐N′‐2‐ethanesulfonic acid (HEPES) buffer without or with MnCl2 (1 mM). The tissue was washed and further incubated with unlabeled myo‐inositol and LiCl (10 mM). Prelabeled slices were then incubated with NE (0.1 mM) or carbachol (1 mM) to induce agonist‐stimulated [3H]PI hydrolysis. Mn2+ treatment resulted in eight‐ and sixfold increases in control levels of [3H]PI and [3H]inositol monophosphate ([3H]IP), respectively. Both NE and carbachol stimulated [3H]IP formation in tissue prelabeled without or with manganese. However, the degree of stimulation (percentage of control values) was greatly attenuated in the presence of Mn2+. In the absence of Mn2+ treatment, NE decreased [3H]PI radioactivity in the tissue to 80% of control values. However, NE did not decrease [3H]PI radioactivity in the Mn2+ ‐treated tissue. These data demonstrate that Mn2+ stimulates incorporation of myo‐[3H]inositol into a pool of PI in brain that has a rapid turnover but is not coupled to agonist‐induced hydrolysis.