| First Author | Oppermann M | Year | 2008 |
| Journal | Am J Physiol Renal Physiol | Volume | 294 |
| Issue | 4 | Pages | F965-70 |
| PubMed ID | 18256308 | Mgi Jnum | J:133508 |
| Mgi Id | MGI:3778723 | Doi | 10.1152/ajprenal.00603.2007 |
| Citation | Oppermann M, et al. (2008) Tubuloglomerular feedback and renin secretion in NTPDase1/CD39-deficient mice. Am J Physiol Renal Physiol 294(4):F965-70 |
| abstractText | Studies in mice with null mutations of adenosine 1 receptor or ecto-5'-nucleotidase genes suggest a critical role of adenosine and its precursor 5'-AMP in tubulovascular signaling. To assess whether the source of juxtaglomerular nucleotides can be traced back to ATP dephosphorylation, experiments were performed in mice with a deficiency in NTPDase1/CD39, an ecto-ATPase catalyzing the formation of AMP from ATP and ADP. Urine osmolarity and glomerular filtration rate (GFR) were indistinguishable between NTPDase1/CD39(-/-) and wild-type (WT) mice. Maximum tubuloglomerular feedback (TGF) responses, as determined by proximal tubular stop flow pressure measurements, were reduced in NTPDase1/CD39(-/-) mice compared with controls (4.2 +/- 0.9 vs. 10.5 +/- 1.2 mmHg, respectively; P = 0.0002). Residual TGF responses gradually diminished after repeated changes in tubular perfusion flow averaging 2.9 +/- 0.9 (on response) and 3.5 +/- 1.1 (off response) mmHg after the second and 2.2 +/- 0.5 (on response) and 1.5 +/- 0.8 (off response) mmHg after the third challenge, whereas no fading of TGF responsiveness was observed in WT mice. Macula densa-dependent and pressure-dependent inhibition of renin secretion, as assessed by acute salt loading and phenylephrine injection, respectively, were intact in NTPDase1/CD39-deficient mice. In summary, NTPDase1/CD39-deficient mice showed a markedly compromised TGF regulation of GFR. These data support the concept of an extracellular dephosphorylation cascade during tubular-vascular signal transmission in the juxtaglomerular apparatus that is initiated by a regulated release of ATP from macula densa cells and results in adenosine-mediated afferent arteriole constriction. |
