Effect of epinephrine on alpha-methyl-D-glucopyranoside uptake in renal proximal tubule cells.

Effect of epinephrine on alpha-methyl-D-glucopyranoside uptake in renal proximal tubule cells. Epinephrine has known to be a very important factor in the regulation of renal sodium excretion. However, the effect of epinephrine on Na+/glucose cotransporter was not fully elucidated. Thus, we examined effect of epinephrine on alpha-methyl-D-glucopyranoside (alpha-MG) uptake and its related signal pathways in the primary cultured rabbit renal proximal tubule cells (PTCs). Epinephrine inhibited alpha-MG uptake in a time- and dose-dependent manner and also decreased SGLT1 and SGLT2 protein level. Both phentolamine and propranolol completely prevented epinephrine-induced inhibition of alpha-MG uptake. The epinephrine-induced inhibition of alpha-MG uptake was blocked by SQ-22536 or myristoylated PKA inhibitor amide 14-22 and epinephrine increased the intracellular cAMP content. In western blotting analysis, epinephrine increases phosphorylation of p44/42 and p38 MAPKs and PD 98059 or SB 203580 blocked the effect of epinephrine. In addition, epinephrine increased AA release and PGE2 production and effects of epinephrine on alpha-MG uptake and AA release were blocked by staurosporine and bisindolylmaleimide I or mepacrine and AACOCF3. Indeed, epinephrine translocated PKC or cPLA2 from cytosol to membrane fraction. In conclusion, epinephrine partially inhibits the alpha-MG uptake through PKA, PKC, p44/42, p38 MAPK, and cPLA2 pathways in the PTCs.