Nucleotide receptors regulate membrane ion transport in renal epithelial cells.
Regulation of plasma membrane ion transport by endogenous purinergic receptors was assessed in a distal renal (A6) cell line. Nucleotide analogues stimulated Na-K-Cl cotransport activity with relative potencies of ATP > UTP > ATP gamma S > 2-methylthio-ATP = alpha,beta-methylene ATP. Activation of nucleotide receptors with extracellular ATP and nucleotide analogues increased intracellular calcium concentration ([Ca2+]i) primarily by release of intracellular calcium stores, with relative potency of agonists similar to that seen for stimulation of Na-K-Cl cotransport. Neither the change in [Ca2+]i nor the stimulation of cotransport was abolished by the adenosine receptor antagonist 8-(4-[N-(2-aminoethyl)carbamoylmethoxy]-phenyl)-1,3-dipropylxanthi ne (XAC). In contrast to the adenosine A2 receptor agonist 5'-N-ethylcarboxamidoadenosine, nucleotide analogues had no discernible effect on cytosolic adenosine 3',5'-cyclic monophosphate levels or adenylyl cyclase activity. To address possible mechanisms for stimulation of Na-K-Cl cotransport by the nucleotide receptor, 125I efflux and patch-clamp studies were used to measure chloride secretion. ATP and ionomycin markedly enhanced 125I efflux and whole cell currents, consistent with activation of chloride conductance pathways. Diphenylamine-2-carboxylate, a chloride channel blocker, eliminated the effects of ionomycin, forskolin, adenosine, and ATP on Na-K-Cl cotransport. This study demonstrates that nucleotide receptors in this model of renal epithelium initiate distinct regulation of Na-K-Cl cotransport. Nucleotide receptors may effect their responses through primary activation of membrane chloride channels.
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Related Subject Headings
- Sodium-Potassium-Chloride Symporters
- Receptors, Purinergic
- Kidney
- Ions
- Intracellular Membranes
- Epithelium
- Epithelial Cells
- Cyclic AMP
- Chlorides
- Cell Membrane
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Sodium-Potassium-Chloride Symporters
- Receptors, Purinergic
- Kidney
- Ions
- Intracellular Membranes
- Epithelium
- Epithelial Cells
- Cyclic AMP
- Chlorides
- Cell Membrane