Chemical hypoxia-induced increases in dopamine D1A receptor mRNA in renal epithelial cells are mediated by nitric oxide

Autor: O. Ashirova, G. Jayaraman, D. P. Healy
Rok vydání: 2000
Předmět:
Zdroj: Acta Physiologica Scandinavica. 168:233-238
ISSN: 0001-6772
Popis: Nitric oxide (NO) and dopamine (DA) have similar effects on renal function, with both having natriuretic and diuretic effects mediated by vascular and tubular mechanisms. Renal ischaemia or hypoxia have been shown to influence the activity of both systems. However, it is not known whether there is any crosstalk between the NO and dopaminergic systems in the kidney. Here using the porcine proximal tubule-like renal epithelial LLC-PK 1 cell line as a model system, we determined whether exposure of cells to chemical hypoxia altered the steady-state levels of D 1A receptor mRNA and whether the changes involved the NO system. Exposure of LLC-PK 1 cells to chemical hypoxia resulted in a marked increase in D 1A receptor mRNA levels as measured by reverse transcription-polymerase chain reaction (RT-PCR). The increased levels of D 1A receptor mRNA following hypoxia were blocked by the NO synthase inhibitors N G -nitro-L-arginine methylester (L-NAME) or N G -monomethyl-L-arginine (L-NMMA). Further evidence that the NO system exerted positive effects on D 1A receptor gene expression came from finding that the NO donor sodium nitroprusside, the NO precursor L-arginine and the guanosine 3',5'-cyclic monophosphate (cyclic GMP) analogue 8-Br-cGMP all increased D 1A receptor mRNA levels in LLC-PK 1 cells. These results indicate that expression of the D 1A receptor in LLC-PK 1 cells can be positively regulated by the NO system. Such an interaction between the renal NO and DA systems may contribute to the reported protective effects that NO and DA exert upon the kidney under conditions of ischaemia.
Databáze: OpenAIRE
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