title: Effect of monoamine uptake inhibitors on norepinephrine-stimulated phosphatidylinositol hydrolysis in rat cortex.
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.
authors.affiliation: Department of Pharmacology, Louisiana State University Medical Center, New Orleans 70112.
authors.forename: M
authors.initials: M
authors.lastname: Mosaddeghi
authors.forename: J M
authors.initials: JM
authors.lastname: Moerschbaecher
authors.forename: R A
authors.initials: RA
authors.lastname: Gonzales
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology*; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D014179:Neurotransmitter Uptake Inhibitors; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; D005473:Fluoxetine; C011386:nisoxetine; D003042:Cocaine; D003891:Desipramine; D009638:Norepinephrine; D011224:Prazosin