Purinergic p2 receptor stimulation attenuates pth inhibition of phosphate uptake by a g protein-dependent mechanism. Lederer, Eleanor D., M. D., Kenneth R. McLeish, M. D. Departments of Medicine and Biochemistry, University of Louisville and the Veterans Administration Medical Center, Louisville, Kentucky, USA
APStracts 2:0030F, 1995.
Purinergic P2 receptors are present on proximal renal tubules, but their function is unknown. Because P2 agonists antagonize vasopressin-stimulated water transport in the distal tubule by inhibiting activation of adenylyl cyclase, we postulated that P2 receptor activation blocks PTH inhibition of phosphate uptake in proximal tubule by preventing PTH-stimulated cAMP generation. PTH inhibition of sodium-dependent phosphate uptake was attenuated by [alpha],[beta]-methylene ATP (AMP-CPP), a P2x receptor agonist, but not by 2methylthio ATP, a P2y receptor agonist, in a dose-dependent manner. AMP-CPP did not attenuate inhibition of phosphate uptake produced by direct activation of adenylyl cyclase with forskolin, by addition of the cAMP analogue 8-bromo-cAMP, or by inhibition of cAMP phosphodiesterase with RO 20-1724. Additionally, AMP-CPP had no effect on basal or PTH-stimulated cAMP production. As PTH also stimulates protein kinase C activation, the effect of AMP-CPP on inhibition of phosphate uptake stimulated by PMA was tested. AMP-CPP had no effect on PMA-induced inhibition of phosphate uptake. Pretreatment with pertussis toxin abolished the attenuating effect of AMP-CPP on PTH inhibition of sodium-dependent phosphate uptake. We conclude that activation of purinergic P2 receptors attenuates the inhibitory effect of PTH on sodium-dependent phosphate uptake by a G protein-dependent mechanism that is independent of cAMP generation, protein kinase A activation, or protein kinase C activation. 

Received 10 June 1994; accepted in final form 27 February 1995.
APS Manuscript Number F195-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 March 1995.