P2 purinoceptor stimulation attenuates PTH inhibition of phosphate uptake by a G protein-dependent mechanism

E. D. Lederer, K. R. McLeish

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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 parathyroid hormone (PTH) inhibition of phosphate uptake in proximal tubule by preventing PTH-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation. PTH inhibition of sodium-dependent phosphate uptake was attenuated by α,β- methylene-ATP (AMP-CPP), a P(2x) receptor agonist, but not by 2-methylthio- ATP, a P(2y) 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 cAP 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 phorbol 12-myristate 13-acetate (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.

Original languageEnglish (US)
Pages (from-to)F309-F316
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume269
Issue number3 38-3
StatePublished - Jan 1 1995
Externally publishedYes

Keywords

  • α,β-methylene adenosine 5'- triphosphate
  • adenylyl cyclase
  • pertussis toxin
  • purinergic receptors

ASJC Scopus subject areas

  • Physiology

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