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.
Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
Eun Jung
EJ
Kim
Yun Jung
YJ
Lee
Jang Hern
JH
Lee
Ho Jae
HJ
Han
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004837:Epinephrine / Q000494:pharmacology* / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008757:Methylglucosides / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000502:physiology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D051297:Sodium-Glucose Transporter 2
D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; C027020:methylglucoside; D011433:Propranolol; D017346:Protein Serine-Threonine Kinases; D004837:Epinephrine; D010646:Phentolamine