TY - JOUR T1 - Regulation of Organic Cation Transport in IHKE-1 and LLC-PK<sub>1</sub> Cells. Fluorometric Studies with 4-(4-Dimethylaminostyryl)N-methylpyridinium JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 305 LP - 310 VL - 286 IS - 1 AU - H. Hohage AU - A. Stachon AU - C. Feidt AU - J. R. Hirsch AU - E. Schlatter Y1 - 1998/07/01 UR - http://jpet.aspetjournals.org/content/286/1/305.abstract N2 - The regulation of transport of the fluorescent organic cation 4-(4-dimethylaminostyryl)-N-methylpyridinium (ASP+) by renal proximal tubular organic cation transport was studied in IHKE-1 and LLC-PK1 cells with a recently established fluorometric technique (Stachon et al., 1996, 1997). Stimulation of Ca++/diacylglycerol-dependent protein kinase by 1,2-dioctanoyl glycerol (DOG; 0.01–1 μmol/l, n = 7), ATP (0.1 mmol/l, n = 9), oxytocin (0.1 μmol/l, n = 6) and bradykinin (1 μmol/l,n = 7) resulted in an increase of ASP+accumulation in IHKE-1 cells by 35 ± 9% (DOG), 65 ± 30% (ATP), 66 ± 14% (bradykinin) and 70 ± 20% (oxytocin) as compared with basal conditions, whereas ASP+ accumulation was slightly reduced in LLC-PK1 cells after stimulation with DOG (1 μmol/l, −20 ± 7%, n = 10) and angiotensin II (0.1 nmol/l, −20 ± 5%, n = 6). ASP+ accumulation in IHKE-1 cells also was increased by 0.5 μmol/l (20 ± 8%, n = 8) and 1 μmol/l forskolin (35 ± 13%, n = 19), and by 8-bromo-cAMP (1 μmol/l, 125 ± 25%, n = 9), both activators of the cAMP-dependent protein kinase (PKA). Activation of the cGMP-dependent protein kinase (PKG) by human atrial natriuretic peptide (10 nmol/l, n = 10) or 8-bromo-cGMP (0.1 mmol/l, n = 12) resulted in an increase of 35 ± 5% and 28 ± 6%, respectively. Activation of PKA and PKG had no influence on ASP+ transport in LLC-PK1cells. Regulation of ASP+ uptake by these two cell lines may be caused by direct phosphorylation of the organic cation transporters involved or by regulation of trafficking of the transporters to the membrane. Differences in the organic cation transporter isoforms or alternatively, in the trafficking may contribute to the distinct regulation of ASP+ transport in IHKE-1 and LLC-PK1 cells. The American Society for Pharmacology and Experimental Therapeutics ER -