Prolonged incubation with desipramine differentially modulate A1A-and A1B-adrenoreceptor signaling in PC12 cells

• Autorzy: Chmielarz P. , Kowalska M. , Rafa-Zablocka K. , Nalepa I.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Action of tricyclic antidepressant drugs (TCA) involves inhibition of noradrenaline re-uptake, however, several of TCA also exhibit affinities for adrenergic receptors (α1-ARs). Furthermore there are reports in literature implying role of α1-AR in depression and antidepressant action. However due to scarcity of selective ligands discriminating the α1-ARs, the specific role of each of three subtypes remains elusive. Aim of current study was to investigate if and how prolonged incubation with desipramine (DMI), a TCA exhibiting affinity for α1-AR could affect the α1A- and α1B-adrenoreceptor reactiveness in vitro. METHODS: Measurements were performed in PC12 cells stably transfected with human α1A- and α1B‑AR. To assess receptor activity cells expressing either one of the receptors were incubated for 24 hours with 10 µM DMI or vehicle. After incubation receptor responsiveness to agonist was assayed by stimulation with serial dilutions of noradrenaline (form 10-9 to 10-4 M) and measurement of inositol phosphate generation with use of TR-FRET based assay. RESULTS: The 24 hours preincubation with DMI shifted the noradrenaline dose response curve rightwards in case of both α1A-AR (EC50 = 0.9 µM and EC50 = 14.5 µM for VEH and DMI preincubated cells, respectively) and α1B‑AR (EC50 = 0.5 µM and EC50 = 2.7 µM, for VEH and DMI preincubated cells, respectively). The effect of DMI was more pronounced for α1A-AR and difference between receptor subtypes was reflected in significant receptor×treatment interaction (P<0.001) in two-way ANOVA comparison. CONCLUSIONS: Our data indicate that DMI can differentially modulate activity of α1A- and α1B‑AR. The diverse susceptibility of α1A- and α1B‑AR to DMI action may be interesting in the light of reports of different role of these receptors in depressive-like behaviors in mice. This study was supported by statutory funds of Institute of Pharmacology, PAS.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S44

Twórcy

autor

Chmielarz P.

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

autor

Kowalska M.

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

autor

Rafa-Zablocka K.

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

autor

Nalepa I.

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