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  • Title: Effect of monoamine uptake inhibitors on norepinephrine-stimulated phosphatidylinositol hydrolysis in rat cortex.
    Author: Mosaddeghi M, Moerschbaecher JM, Gonzales RA.
    Journal: Biochem Pharmacol; 1989 Jan 15; 38(2):257-62. PubMed ID: 2536541.
    Abstract:
    The effects of the monoamine uptake inhibitors cocaine, nisoxetine, and desipramine (DMI) on norepinephrine (NE) stimulated phosphatidylinositol (PI) hydrolysis were investigated. Rat cortical tissue slices were labeled with [3H]inositol. Slices were then stimulated, in vitro, with NE in LiCl containing buffer in the presence and absence of monoamine uptake inhibitors. Cocaine and nisoxetine, but not DMI, potentiated NE-stimulated PI hydrolysis with a significant decrease in the EC50. Nisoxetine appeared to be more potent than cocaine with respect to the potentiation of NE-stimulated PI hydrolysis. The potentiating effect of cocaine was biphasic and dependent upon the concentrations of cocaine and NE. The NE concentration-effect curve was shifted to the right 100-fold in the presence of 0.1 microM prazosin. Cocaine at 10 microM did not potentiate NE-stimulated PI hydrolysis in the presence of 0.1 microM prazosin. Cocaine at 10 microM did not affect significantly the binding of [3H]prazosin or the NE-[3H]prazosin competition binding to cortical membranes. The results suggest that NE-uptake inhibition by cocaine and nisoxetine is the mechanism for the enhancement of NE-stimulated PI hydrolysis.
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