Luminal adenosine receptors regulate amiloride-sensitive Na+ channels in A6 distal nephron cells.
To investigate the effects of luminal adenosine on amiloride-sensitive Na+ channels, we applied the cell-attached patch-clamp technique to A6 distal nephron cells. Exposure to luminal 30 nM adenosine increased number of channels x open probability (NP0) from 0.38 +/- 0.08 to 0.77 +/- 0.09 (means +/- SE; P < 0.01, n = 17). Luminal exposure to an A1-receptor antagonist (30 nM 8-cyclopentyl-1,3-dipropylxanthine) abolished (P = 0.17, n = 11), whereas an A1 agonist (30 nM N6-cyclohexyladenosine) reproduced (P < 0.02, n = 6) the stimulatory effect of 30 nM adenosine. In contrast, higher concentrations of luminal adenosine (1 or 10 microM) decreased NP0 from 0.65 +/- 0.09 to 0.24 +/- 0.10 (P < 0.02, n = 11) and from 0.80 +/- 0.11 to 0.19 +/- 0.03 (P < 0.01, n = 8), respectively. Channel inhibition by high-dose luminal adenosine was abolished by an A2 antagonist (30 microM 3,7-dimethyl-1-propargylxanthine; P = 0.2, n = 10) and mimicked by an A2 agonist (100 nM CGS-21680 hydrochloride; P < 0.0005, n = 8). We conclude that 1) purinergic regulation of distal nephron Na+ channels is mediated by stimulatory apical A1 receptors and inhibitory apical A2 receptors; 2) basal urinary adenosine concentrations (in nM) would stimulate Na+ reabsorption, whereas higher urinary concentrations (in microM), e.g., renal ischemia and elevations in filtered NaCl load, would increase Na+ excretion; and 3) urinary adenosine may be involved in feedback regulation of distal nephron Na+ transport.
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Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
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D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D009399:Nephrons / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010627:Phenethylamines / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects*; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D015222:Sodium Channels; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C057837:3,7-dimethyl-1-propargylxanthine; D000584:Amiloride; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D013805:Theobromine