Haloperidol effect on intracellular signals system coupled to alpha1-adrenergic receptor in rat cerebral frontal cortex.
The induction of intracellular signals coupled to alpha1-adrenoceptor by haloperidol, were studied in rat cerebral frontal cortex. The neuroleptic exerts a biphasic effect on nitric oxide synthase (NOS), inhibiting the enzymatic activity at low concentrations (10(-9) M), while higher concentrations (10(-5) M) increased it. Protein kinase C (PKC) and phosphoinositol turnover (PIs) were involved in these actions, as haloperidol induced PKC translocation at low concentrations, and increased PIs turnover at high concentrations. All the effects of haloperidol were blocked by the alpha-adrenoceptor antagonist prazosin and the phospholipase C (PLC) inhibitor NCDC. The possibility that a cross-talk between both enzymatic pathways depending on the neuroleptic concentration used in rat cerebral frontal cortex, is also discussed.
Borda
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Centro de Estudios Farmacológicos y Botánicos (CEFYBO-CONICET), Buenos Aires, Argentina.
Genaro
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AM
Cremaschi
G
G
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D046508:Culture Techniques; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D007295:Inositol Phosphates; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D011493:Protein Kinase C; D006220:Haloperidol