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. Extracellular nucleotides regulate renal transport. A luminal P2Y 2  receptor in mouse cortical collecting duct (CCD) principal cells has been demonstrated elsewhere. Herein the effects of adenosine triphosphate (ATP) and uridine triphosphate (UTP) on electrogenic Na +  absorption in perfused CCD of mice kept on a low-NaCl diet were investigated. Simultaneously, transepithelial voltage ( V  te ), transepithelial resistance ( R  te ), and fura-2 [Ca 2+ ] i  fluorescence were measured. Baseline parameters were  V  te , −16.5 ± 1.2 mV;  R  te , 80.8 ± 7.1 Ω cm 2 ; and equivalent short-circuit current ( I  sc ), −261.0 ± 25.1 μA/cm 2  ( n  = 45). Amiloride (10 μM) almost completely inhibited  I  sc  to −3.9 ± 3.8 μA/cm 2  ( n  = 10). Luminal ATP (100 μM) reduced  V  te  from −16.5 ± 2.1 to −12.5 ± 1.93 and increased  R  te  from 113.1 ± 16.2 to 123.8 ± 16.7 Ω cm 2 , which resulted in a 31.7% inhibition of amiloride-sensitive  I  sc  ( n  = 12). Similarly, luminal UTP reversibly reduced  V  te  from −22.0 ± 2.1 to −13.6 ± 2.1 mV and increased  R  te  from 48.4 ± 5.3 to 59.2 ± 7.1 Ω cm 2 , which resulted in 49.1% inhibition of Na +  absorption ( n  = 6). In parallel, luminal ATP and UTP elevated [Ca 2+ ] i  in CCD, increasing the fura-2 ratio by 2.7 ± 0.7 and 4.0 ± 1.2, respectively. Basolateral ATP and UTP (100 μM) also inhibited amiloride-sensitive  I  sc  by 21.8 ( n  = 14) and 20.1% ( n  = 8), respectively. Inhibition of luminal nucleotide-induced [Ca 2+ ] i  increase by Ca 2+  store depletion with cyclopiazonic acid (3 μM) did not affect nucleotide-mediated inhibition of Na +  transport ( n  = 7). No evidence indicated the activation of a luminal Ca 2+ -activated Cl −  conductance, a phenomenon previously shown in M-1 CCD cells ( J Physiol  524: 77–99, 2000). In essence, these data indicate that luminal ATP and UTP, most likely via P2Y 2  receptors, mediate inhibition of amiloride-sensitive I sc  in perfused mouse CCD. This inhibition appears to occurs independently of an increase of cytosolic Ca 2+ .

Luminal P2Y2 Receptor-Mediated Inhibition of Na+ Absorption in Isolated Perfused Mouse CCD