The effect of prolonged imipramine treatment on the alpha 1-adrenoceptor-induced translocation of protein kinase C in the central nervous system in rats.
The aim of the study was to investigate the effects of prolonged treatment with imipramine (10 mg kg-1/day i.p. for 21 days) on the translocation of protein kinase C (PKC) after stimulation of the alpha 1-adrenoceptor. Methoxamine (5-50 mg kg-1) and phenylephrine (0.1-1 mg kg-1) induced a rapid and long-term redistribution of PKC from the cytosolic to the membrane fraction in the rat frontal cortex and hippocampus. The effects of methoxamine and phenylephrine were completely blocked by pretreatment with prazosin. Prolonged pretreatment with imipramine changed the response of PKC to methoxamine and phenylephrine. Much lower doses of alpha 1-adrenoceptor agonists were able to induce the redistribution of PKC. Moreover, prolonged treatment with imipramine markedly increased the basal activity of PKC in the membrane fractions of the frontal cortex and hippocampus.
Szmigielski
A
A
Department of Pharmacodynamics, Medical University of Lodz, Poland.
Górska
D
D
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*
D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D011493:Protein Kinase C; D008729:Methoxamine; D007099:Imipramine