ATP inhibits the hydrosmotic effect of AVP in rabbit CCT: evidence for a nucleotide P2u receptor.
In rabbit renal cortical collecting tubule (CCT), perfused in vitro at 38 degrees 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 = alpha, beta-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-bromoadenosine 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.
Rouse
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Department of Medicine, Baylor College of Medicine, Houston, Texas.
Leite
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Suki
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D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005260:Female; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007685:Kidney Tubules, Collecting / Q000187:drug effects* / Q000378:metabolism*; D009995:Osmosis / Q000187:drug effects; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D058914:Purinergic Antagonists; D011817:Rabbits; D011983:Receptors, Purinergic / Q000145:classification / Q000378:metabolism*; D019311:Staurosporine; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014867:Water / Q000378:metabolism*
D000470:Alkaloids; D002121:Calcium Channel Blockers; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D010566:Virulence Factors, Bordetella; D014867:Water; D001127:Arginine Vasopressin; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019311:Staurosporine