Document Detail

Na(+)/H(+) exchanger activity and dopamine D(1)-like receptor function in two opossum kidney cell clonal sublines.
MedLine Citation:
PMID:  12438762     Owner:  NLM     Status:  MEDLINE    
BACKGROUND/AIMS: The enhanced renal reabsorption of Na(+) in hypertension is accompanied by a defective transduction of the renal dopamine D(1) receptor signal. The present study evaluated the response of the Na(+)/H(+) exchanger to dopamine D(1)-like receptor stimulation in two clonal subpopulations of opossum kidney (OK) cells (OK(LC) and OK(HC)) that are functionally different with respect to their ability to transport Na(+). METHODS: Na(+)/H(+) exchanger activity was assayed as the initial rate of intracellular pH (pH(i)) recovery after an acid load. The presence of D(1)-like receptors was measured in saturation experiments with [(3)H]-Sch 23390 in cell membranes. RESULTS: V(max) values (in pH units/s) for Na(+)-dependent pH(i) recovery in OK(HC) cells (0.00521+/-0.0004) were twice those in OK(LC) (0.00202+/-0.0001), with similar K(m) values. The selective D(1)-like receptor agonist SKF 38393 (30 to 3000 nM) attenuated the Na(+)/H(+) exchanger activity in OK(HC) cells more potently than in OK(LC) cells.GTPgammaS and forskolin were equipotent in inhibiting the Na(+)/H(+) exchanger in OK(HC) cells and OK(LC) cells. The SKF 38393-induced increase in cyclic AMP levels in OK(HC) cells was greater than in OK(LC) cells. B(max) values for the binding of [(3)H]-Sch 23390 in OK(HC) cells were twice that in OK(LC) cells, with similar K(D) values. The abundance of G(Salpha) protein in cell membranes of OK(HC) cells was similar to that in OK(LC) cells. CONCLUSION: The enhanced sensitivity of the Na(+)/H(+) exchanger to inhibition by the D(1)-like receptor agonist in OK(HC) cells correlated positively with the high density of D(1)-like binding sites and the enhanced production of cyclic AMP during D(1)-like receptor stimulation in OK(HC) cells.
Pedro Gomes; Patrício Soares-da-Silva
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology     Volume:  12     ISSN:  1015-8987     ISO Abbreviation:  Cell. Physiol. Biochem.     Publication Date:  2002  
Date Detail:
Created Date:  2002-11-19     Completed Date:  2003-06-10     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9113221     Medline TA:  Cell Physiol Biochem     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  259-68     Citation Subset:  IM    
Copyright Information:
Copyright 2002 S. Karger AG, Basel
Institute of Pharmacology Therapeutics, Faculty of Medicine, Porto, Portugal.
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MeSH Terms
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / analogs & derivatives,  pharmacology
Amiloride / analogs & derivatives,  pharmacology
Benzazepines / chemistry,  metabolism
Binding Sites
Biological Transport / drug effects,  physiology
Clone Cells
Cyclic AMP / metabolism
Dopamine Agonists / pharmacology
Dopamine Antagonists / pharmacology
Enzyme Inhibitors / pharmacology
GTP-Binding Protein alpha Subunits, Gs / analysis,  metabolism
Hydrogen-Ion Concentration
Kidney / cytology,  metabolism*
Opossums / metabolism*
Receptors, Dopamine D1 / metabolism*
Sodium-Hydrogen Antiporter / antagonists & inhibitors,  metabolism*
Reg. No./Substance:
0/Benzazepines; 0/Dopamine Agonists; 0/Dopamine Antagonists; 0/Enzyme Inhibitors; 0/Receptors, Dopamine D1; 0/Sodium-Hydrogen Antiporter; 10028-17-8/Tritium; 2609-46-3/Amiloride; 60-92-4/Cyclic AMP; 67287-49-4/2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; EC Protein alpha Subunits, Gs

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