Imipramine-induced changes in expression of G proteins and ERKs in cerebral cortex of rat

• Autorzy: Wieczorek K. , Bielawski A. , Zalewska T. , Nalepa I.
• Języki publikacji: EN

Abstrakty

EN

Imipramine belongs to a class of tricyclic antidepressants which augment monoaminergic transmission in a brain and are prevailingly used in treatment of depressive disorders. Increased availability of neurotransmitters (e.g., noradrenaline and serotonin) results among others, in modulation of the activity of G protein-coupled receptors and other proteins involved in intracellular signaling. The study was aimed to assess the effects of single and repetitive treatment with imipramine (10 mg/kg, twice daily, for 21 days) on the expression of G11, GQ and G12 proteins and protein kinases, ERK1/ERK2 and pERK1/pERK2 in the rat prefrontal cortex. Animals were sacrifi ced 4 and 24 h after the last drug injection. Single and chronic treatments with imipramine decreased similarly the Gq protein level (by 29, 36 and 48%), while G11 and G12 were unchanged. In contrast, the acute imipramine dose increased the level of ERK1 (by 32% above saline control) that was further enhanced by the chronic treatment (by 48% and 64%, respectively). The increase in ERK2 level was similarly marked (at both time-points) after chronic (by 39% and 31%) and after single dose of drug (by 28% vs. saline). Interestingly, the ERK1/ERK2 ratio was changed only at 24 h after completion of chronic treatment (127% vs. saline control). The same direction of changes, independently on amount of imipramine doses, was observed in the case of pERK1 and pERK2 (increase by approx. 25% of saline group). Our data demonstrate that treatment with imipramine causes downregulation of Gq protein level and upregulates the ERK1/ERK2 pathway(s). The results suggest that imipramine-induced changes in ERKs can result from other than Gq-linked intracellular signaling. Supported by Polish MNSW Scientifi c Network fund.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.84

Twórcy

autor

Wieczorek K.

• Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Bielawski A.

• Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

autor

Zalewska T.

• NeuroRepair Department, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

autor

Nalepa I.

• Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland