The role of P2Y-receptors in the regulation of glomerular volume.
BACKGROUND
Extracellular ATP signaling affects the cells of renal glomeruli via activation of P2-purinoceptors, denoted as P2X and P2Y. Through either of these purinoceptors, ATP is able to stimulate an increase in intracellular [Ca2+]. P2Y-receptors are expressed on mesangial and endothelial 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 generation of adenosine. The aim of the present study was to investigate the involvement of P2Y-receptors in responses of renal glomeruli to extracellular ATP.


METHODS
Renal glomeruli were isolated from rats by 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 adenosine concentration in the incubation mixture were measured using luminometric methods.


RESULTS
Extracellular ATP (1 microM) induced relaxation of Ang II-precontracted glomeruli in time-dependent manner. The glomeruli relaxed completely at 2nd minute of incubation. The relaxation was considerably diminished at 5th minute of incubation as compared to 2nd minute. Relaxing effect was completely prevented by an antagonist of P2Y-receptors i.e. reactive blue 2. The decrease in ATP concentration with time was accompanied by a rise 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 minute of incubation but there was no effect at 5th minute of incubation.


CONCLUSIONS
The extracellular ATP through activation of P2Y-receptors may regulate the volume of renal glomeruli, which in turn influences on the glomerular filtration rate, through at least two mechanisms: one is ATP-dependent glomerular relaxation in the initiate phase and the other is glomerular contraction caused by either ATP itself or adenosine formed from ATP hydrolysis in maintenance phase.
Jankowski
M
M
Department of Clinical Chemistry, Medical University of Gdańsk, Poland. majank@amg.gda.pl
Szczepańska-Konkel
M
M
Kalinowski
L
L
Angielski
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D007678:Kidney Glomerulus / Q000033:anatomy & histology* / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000378:metabolism / Q000502:physiology*
D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate