Effect of monoamine uptake inhibitors on norepinephrine-stimulated phosphatidylinositol hydrolysis in rat cortex.
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.
Mosaddeghi
M
M
Department of Pharmacology, Louisiana State University Medical Center, New Orleans 70112.
Moerschbaecher
J M
JM
Gonzales
R A
RA
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
D014179:Neurotransmitter Uptake Inhibitors; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; D005473:Fluoxetine; C011386:nisoxetine; D003042:Cocaine; D003891:Desipramine; D009638:Norepinephrine; D011224:Prazosin