The role of protein kinase C and cyclic AMP in the ammonia-induced shift of the taurine uptake/efflux balance towards efflux in C6 cells.
A previous study showed that treatment of C6 glioma cells with 10 mM ammonium chloride monia") for 24 h decreases taurine uptake and evokes sodium-dependent taurine efflux, indicating reversal of the taurine transporter (TauT)-mediated transport as an underlying mechanism. Consistent with the involvement of TauT we now show that the ammonia-induced changes in Tau uptake and efflux are inhibited by the protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDBu). Ammonia treatment of C6 cells resulted in increased intracellular accumulation of cAMP. Incubation of the cells with dibutyryl cAMP (dbcAMP) mimicked the effects of ammonia on both taurine uptake and efflux. The effects of dbcAMP on taurine uptake and efflux were additive to the effects of ammonia. Collectively, the results suggest that the effects of ammonia on taurine uptake and efflux may be partly mediated by cAMP. Consistent with this mechanism, the adenyl cyclase inhibitor, miconazole reduced the stimulation of efflux by ammonia.
Zielińska
Magdalena
M
Department of Neurotoxicology, Medical Research Centre, Polish Academy of Sciences, Pawińskiego St. 5, 02-106, Warsaw, Poland.
Zabłocka
Barbara
B
Dybel
Anna
A
Albrecht
Jan
J
D000641:Ammonia / Q000494:pharmacology*; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000502:physiology*; D020536:Enzyme Activators / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D013654:Taurine / Q000378:metabolism*
D020536:Enzyme Activators; D009419:Nerve Tissue Proteins; D013654:Taurine; D015240:Phorbol 12,13-Dibutyrate; D003994:Bucladesine; D000641:Ammonia; D000242:Cyclic AMP; D011493:Protein Kinase C