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Maciej Jankowski, Mirosława Szczepańska-Konkel, Leszek Kalinowski, Stefan Angielski
Med Sci Monit 2001; 7(4): BR635-340
BACKGROUND: Extracellular ATP signaling affects the cells of renal glomerulivia activation of P2-purinoceptors, denoted as P2X and P2Y. Through either of these purinoceptors, ATPis able to stimulate an increase in intracellular [Ca2+]. P2Y-receptors are expressed on mesangial andendothelial cells, thus may participate in contraction and relaxation of glomeruli, respectively. Moreover,P2Y-receptors possess activity of ecto-ATPase which may lead to dephosphorylation of ATP and generationof adenosine. The aim of the present study was to investigate the involvement of P2Y-receptors in responsesof renal glomeruli to extracellular ATP.
MATERIAL AND METHODS: Renal glomeruli were isolated from ratsby sieving technique. [3H]-inulin was used to measure the intracapillary volume of isolated glomeruli.Changes of intracapillary volume reflect contraction and relaxation of the glomeruli. ATP and adenosineconcentration in the incubation mixture were measured using luminometric methods.
RESULTS: ExtracellularATP (1 microM) induced relaxation of Ang II-precontracted glomeruli in time-dependent manner. The glomerulirelaxed completely at 2nd minute of incubation. The relaxation was considerably diminished at 5th minuteof incubation as compared to 2nd minute. Relaxing effect was completely prevented by an antagonist ofP2Y-receptors i.e. reactive blue 2. The decrease in ATP concentration with time was accompanied by arise in adenosine concentration which led to contraction of glomeruli. Non-metabolised analogue of ATP,an agonist of P2Y-receptors i.e. 2-methylthio-ATP (1 microM) induced complete relaxation at 2nd minuteof incubation but there was no effect at 5th minute of incubation.
CONCLUSIONS: The extracellular ATPthrough activation of P2Y-receptors may regulate the volume of renal glomeruli, which in turn influenceson the glomerular filtration rate, through at least two mechanisms: one is ATP-dependent glomerular relaxationin the initiate phase and the other is glomerular contraction caused by either ATP itself or adenosineformed from ATP hydrolysis in maintenance phase.