Document Detail

Paracrine stimulation of vascular smooth muscle proliferation by diadenosine polyphosphates released from proximal tubule epithelial cells.
MedLine Citation:
PMID:  17361116     Owner:  NLM     Status:  MEDLINE    
The purinergic receptor system plays an important role in the regulation of both vascular and tubular functions within the kidney; however, the release of purinergic agonists other than ATP by renal tissue is not known. In this investigation, we determine if kidney tissue is a source of diadenosine polyphosphates, which have high affinity for the P(2X) and P(2Y) receptors. Both diadenosine pentaphosphate and hexaphosphate were identified by matrix-assisted laser desorption ionization-mass spectrometry in extracts purified from both whole porcine kidney and from cloned cells of the LLC-PK1 cell line. Both polyphosphates in nanomolar concentrations were found to significantly stimulate the proliferation of vascular smooth muscle cells derived from rat thoracic aortas. The purinergic-receptor antagonist, suramin, did not significantly affect the growth-stimulatory properties of the polyphosphates. The growth stimulation of vascular smooth muscle cells by platelet-derived growth factor was potentiated by both diadenosine polyphosphates. We conclude that diadenosine polyphosphates are endogenous purinergic agonists of the kidney that have physiologic and pathophysiologic relevance. These epithelial cell metabolic products have vasoregulatory properties while linking the energy supply and tubular function.
V Jankowski; S Karadogan; R Vanholder; J-R Nofer; S Herget-Rosenthal; M van der Giet; M Tölle; T N A Tran; W Zidek; J Jankowski
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Publication Detail:
Type:  Journal Article     Date:  2007-03-14
Journal Detail:
Title:  Kidney international     Volume:  71     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-05-14     Completed Date:  2007-09-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  994-1000     Citation Subset:  IM    
Charité, Medizinische Klinik IV (CBF), Berlin, Germany.
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MeSH Terms
Aorta, Thoracic / cytology
Cell Proliferation* / drug effects
Cells, Cultured
Dinucleoside Phosphates / metabolism,  pharmacology,  physiology*
Drug Synergism
Epithelial Cells / metabolism
Kidney Tubules, Proximal / cytology,  metabolism*
Muscle, Smooth, Vascular / cytology*
Myocytes, Smooth Muscle / cytology*
Paracrine Communication / physiology*
Platelet-Derived Growth Factor / pharmacology
Rats, Inbred WKY
Rats, Sprague-Dawley
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Reg. No./Substance:
0/Dinucleoside Phosphates; 0/Platelet-Derived Growth Factor; 50304-44-4/P(1),P(5)-di(adenosine-5'-)pentaphosphate; 56983-23-4/diadenosine 5',5''''-P1,P6-hexaphosphate

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