Dopamine D2 receptor stimulation of Na+/H+ exchange assessed by quantification of extracellular acidification

K. A. Neve, M. R. Kozlowski, M. P. Rosser

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

A microphysiometer was used to quantify the rate of extracellular acidification by C6 glioma cells and L fibroblasts expressing recombinant dopamine D2 receptors. The dopamine D2 receptor agonist, quinpirole, accelerated the rate of acidification of the medium by C6 cells expressing either the short or long form of D2 receptors, D2415 and D2444, but not by wild-type cells that were not transfected with a D2 receptor cDNA. The rate of acidification increased with increasing concentrations of quinpirole up to 100 nM. Inhibition of the response by the dopamine D2 antagonist, spiperone, provided additional evidence that the enhanced extracellular acidification resulted from stimulation of D2 receptors. To test the hypothesis that D2 receptor-stimulated extracellular acidification was due to transport of protons by a Na+/H+ antiporter and reflected intracellular alkalinization, the effect of two inhibitors of Na+/H+ exchange, amiloride and methyl-isobutyl-amiloride, was determined. Both compounds inhibited quinpirole-induced extracellular acidification at concentrations that did not alter D2 receptor-mediated inhibition of adenylylcyclase or radioligand binding to D2 receptors. In addition, quinpirole-induced extracellular acidification was greatly inhibited by removal of sodium from the extracellular medium, confirming the participation of Na+/H+ exchange in the extrusion of acid. Quinpirole (100 nM) also increased the rate of extracellular acidification by L cells expressing D2415, LZR1 cells. Treatment with pertussis toxin (100 ng/ml for 18 h) had no effect on the quinpirole-induced acid extrusion by C6D2415 and LZR1 cells, although the same pertussis toxin treatment regimen completely prevented inhibition of adenylylcyclase. We conclude that recombinant D2 receptors accelerate Na+/H+ exchange in C6 cells and L fibroblasts by a pathway that does not involve inhibition of adenylylcyclase or pertussis toxin-sensitive G proteins.

Original languageEnglish (US)
Pages (from-to)25748-25753
Number of pages6
JournalJournal of Biological Chemistry
Volume267
Issue number36
StatePublished - Dec 1 1992

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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