Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.12 (PKG)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 mumol/l, n = 7), ATP (0.1 mmol/l, n = 9), oxytocin (0.1 mumol/l, n = 6) and bradykinin (1 mumol/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 mumol/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 mumol/l (20 +/- 8%, n = 8) and 1 mumol/l forskolin (35 +/- 13%, n = 19), and by 8-bromo-cAMP (1 mumol/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-PK1 cells. 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.
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PMID:Regulation of organic cation transport in IHKE-1 and LLC-PK1 cells. Fluorometric studies with 4-(4-dimethylaminostyryl)-N-methylpyridinium. 965 73

In collecting duct principal cells, aquaporin 2 (AQP2) is shuttled from intracellular vesicles to the plasma membrane upon vasopressin (VP) stimulation. VP activates adenylyl cyclase, increases intracellular cAMP, activating protein kinase A (PKA) to phosphorylate AQP2 on the COOH-terminal residue, serine 256. Using rat kidney slices and LLC-PK1 cells stably expressing AQP2 (LLC-AQP2 cells), we now show that AQP2 trafficking can be stimulated by cAMP-independent pathways. In these systems, the nitric oxide (NO) donors sodium nitroprusside (SNP) and NONOate and the NO synthase substrate L-arginine mimicked the effect of VP, stimulating relocation of AQP2 from cytoplasmic vesicles to the plasma membrane. Unlike VP, these other agents did not increase intracellular cAMP. However, SNP increased intracellular cGMP, and exogenous cGMP stimulated AQP2-membrane insertion. Atrial natriuretic factor, which signals via cGMP, also stimulated AQP2 translocation. The VP and SNP effects were blocked by the kinase inhibitor H89. SNP did not stimulate membrane insertion of AQP2 in LLC-PK1 cells expressing the phosphorylation-deficient mutant 256SerAla-AQP2, indicating that phosphorylation of Ser256 is required for signaling. Both PKA and cGMP-dependent protein kinase G phosphorylated AQP2 on this COOH-terminal residue in vitro. These results demonstrate a novel, cAMP-independent and cGMP-dependent pathway for AQP2 membrane insertion in renal epithelial cells.
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PMID:Nitric oxide and atrial natriuretic factor stimulate cGMP-dependent membrane insertion of aquaporin 2 in renal epithelial cells. 1106 64