ATP inhibits the hydrosmotic effect of AVP in rabbit CCT: Evidence for a nucleotide P2u receptor

D. Rouse, M. Leite, W. N. Suki

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

In rabbit renal cortical collecting tubule (CCT), perfused in vitro at 38°C, ATP in concentrations of 10-7 M and greater inhibits arginine vasopressin (AVP)-stimulated osmotic water permeability (Pf). The P1-purinergic receptor antagonist 8-phenyltheophylline did not attenuate the inhibitory action of ATP, and the poorly hydrolyzable ATP analogue, 5'-adenylylimidodiphosphate (AMP-PNP), mimicked the effect of ATP, arguing against an effect of ATP on a P1 receptor or the "P site." Purinergic receptor agonists inhibited AVP-stimulated Pf with the following rank order efficacy: ATP = ADP = UTP = AMP-PNP = α,β-methylene-ATP > 2-methylthio-ATP ≫ AMP > adenosine, consistent with the pharmacology of a "nucleotide" receptor subtype. Pertussis toxin pretreatment attenuated the action of 10-5 and 10-6 MATP; however, 10-4 MATP failed to inhibit the hydrosmotic action of forskolin or 8-bromoadeno-sine 3',5'-cyclic monophosphate. Pretreatment with the phosphodiesterase inhibitor RO20-1724 or indomethacin did not inhibit the action of ATP. Staurosporin and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester significantly attenuated the inhibition of Pf by lower concentrations of ATP. These data suggest that ATP activates nucleotide receptors on the CCT, mobilizing intracellular Ca2+, which inhibits the hydrosmotic action of AVP.

Original languageEnglish
Pages (from-to)F289-F295
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume267
Issue number2 36-2
StatePublished - Dec 1 1994

Keywords

  • Adenylyl cyclase
  • Arginine vasopressin
  • Intracellular ionized calcium
  • Pertussis toxin
  • Prosta-glandins
  • Protein kinase C

ASJC Scopus subject areas

  • Physiology

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