| First Author | Ardaillou N | Year | 1999 |
| Journal | Kidney Int | Volume | 55 |
| Issue | 4 | Pages | 1293-302 |
| PubMed ID | 10200993 | Mgi Jnum | J:57178 |
| Mgi Id | MGI:1344059 | Doi | 10.1046/j.1523-1755.1999.00393.x |
| Citation | Ardaillou N, et al. (1999) Mesangial cells from diabetic NOD mice constitutively express increased density of atrial natriuretic peptide C receptors. Kidney Int 55(4):1293-302 |
| abstractText | BACKGROUND: Experimental evidence shows that natriuretic peptides (NPs) play a pathophysiological role in the glomerular hemodynamic abnormalities that occur in diabetes mellitus. METHODS: In this study, the cGMP response to NPs and the different subtypes of NP receptors were examined in mesangial cells derived from a genetic model of diabetes, the nonobese diabetic (NOD) mouse. Multiple mesangial cell lines were derived from diabetic (D-NOD) and nondiabetic (ND-NOD) adult mice and were studied at different passages. RESULTS: cGMP accumulation after stimulation by atrial NP (ANP) or C-type NP (CNP) was markedly inhibited in D-NOD cells irrespective of the glucose concentration (6 or 20 mM) in the culture medium. In contrast, NP receptor density measured from [125I]-ANP saturation binding curves was 7.5 times greater in D-NOD than in ND-NOD cells. No change in KD (200 pM in both cell lines) was observed. Competitive inhibition studies showed that 4-23 C-ANP, which is specific of clearance receptors (NPR-C), displaced 90% of the maximum fraction bound, suggesting the predominance of NPR-C in both cell lines. Further identification was obtained from RNase protection assay and reverse transcription-polymerase chain reaction, which also demonstrated the higher expression of NPR-C mRNA in D-NOD cells. In contrast, NPR-A mRNA was not modified. Increased expression of NPR-C in D-NOD cells was associated with an increase of ANP internalization rate at 37 degrees C, indicating that these receptors were functional. CONCLUSIONS: These studies demonstrate that the constitutive overexpression of NPR-C in D-NOD mesangial cells is associated with a decreased response of cGMP to ANP or CNP treatment. This could be due to the lesser availability of the peptides for binding to NPR-A or NPR-B or to an inhibitory effect on NP-dependent guanylate cyclase activity via the activation of NPR-C. |
