Differential inhibition of secretagogue-stimulated sodium uptake in adrenal chromaffin cells by activation of D4 and D5 dopamine receptors

Mary K. Dahmer, Susan Senogles

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Abstract

Recent studies have demonstrated that D1-selective and D2-selective dopamine receptor agonists inhibit catecholamine secretion and Ca2+ uptake into bovine adrenal chromaffin cells by receptor subtypes that we have identified by PCR as D5, a member of the D1-like dopamine receptor subfamily, and D4, a member of the D2-like dopamine receptor subfamily. The purpose of this study was to determine whether activation of D5 or D4 receptors inhibits influx of Na+, which could explain inhibition of secretion and Ca2+ uptake by dopamine agonists. D1-selective agonists preferentially inhibited both dimethylphenylpiperazinium- (DMPP) and veratridine-stimulated 22Na+ influx into chromaffin cells. The D1-selective agonists chloro-APB hydrobromide (Cl- APB; 100 μM) and SKF-38393 (100 μM) inhibited DMPP-stimulated Na+ uptake by 87.5 ± 2.3 and 59.7 ± 4.5%, respectively, whereas the D2-selective agonist bromocriptine (100 μM) inhibited Na+ uptake by only 22.9 ± 5.0%. Veratridine-stimulated Na+ uptake was inhibited 95.1 ± 3.2 and 25.7 ± 4.7% by 100 μM Cl-APB or bromocriptine, respectively. The effect of Cl-APB was concentration dependent. A similar IC50 (~18 μM) for inhibition of both DMPP- and veratridine-stimulated Na+ uptake was obtained. The addition of 8- bromo-cyclic AMP (1 mM) had no effect on either DMPP- or veratridine- stimulated Na+ uptake. These observations suggest that D1-selective agonists are inhibiting secretagogue-stimulated Na+ uptake in a cyclic AMP- independent manner.

Original languageEnglish (US)
Pages (from-to)1960-1964
Number of pages5
JournalJournal of Neurochemistry
Volume67
Issue number5
StatePublished - Nov 1996

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Dopamine D5 Receptors
Dimethylphenylpiperazinium Iodide
Dopamine D4 Receptors
Veratridine
Chromaffin Cells
Sodium
Chemical activation
Bromocriptine
Dopamine Agonists
Dopamine Receptors
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
8-Bromo Cyclic Adenosine Monophosphate
Dopamine D1 Receptors
Dopamine D2 Receptors
Cyclic AMP
Inhibitory Concentration 50
Catecholamines
Polymerase Chain Reaction
SK&F 82958

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

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title = "Differential inhibition of secretagogue-stimulated sodium uptake in adrenal chromaffin cells by activation of D4 and D5 dopamine receptors",
abstract = "Recent studies have demonstrated that D1-selective and D2-selective dopamine receptor agonists inhibit catecholamine secretion and Ca2+ uptake into bovine adrenal chromaffin cells by receptor subtypes that we have identified by PCR as D5, a member of the D1-like dopamine receptor subfamily, and D4, a member of the D2-like dopamine receptor subfamily. The purpose of this study was to determine whether activation of D5 or D4 receptors inhibits influx of Na+, which could explain inhibition of secretion and Ca2+ uptake by dopamine agonists. D1-selective agonists preferentially inhibited both dimethylphenylpiperazinium- (DMPP) and veratridine-stimulated 22Na+ influx into chromaffin cells. The D1-selective agonists chloro-APB hydrobromide (Cl- APB; 100 μM) and SKF-38393 (100 μM) inhibited DMPP-stimulated Na+ uptake by 87.5 ± 2.3 and 59.7 ± 4.5{\%}, respectively, whereas the D2-selective agonist bromocriptine (100 μM) inhibited Na+ uptake by only 22.9 ± 5.0{\%}. Veratridine-stimulated Na+ uptake was inhibited 95.1 ± 3.2 and 25.7 ± 4.7{\%} by 100 μM Cl-APB or bromocriptine, respectively. The effect of Cl-APB was concentration dependent. A similar IC50 (~18 μM) for inhibition of both DMPP- and veratridine-stimulated Na+ uptake was obtained. The addition of 8- bromo-cyclic AMP (1 mM) had no effect on either DMPP- or veratridine- stimulated Na+ uptake. These observations suggest that D1-selective agonists are inhibiting secretagogue-stimulated Na+ uptake in a cyclic AMP- independent manner.",
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N2 - Recent studies have demonstrated that D1-selective and D2-selective dopamine receptor agonists inhibit catecholamine secretion and Ca2+ uptake into bovine adrenal chromaffin cells by receptor subtypes that we have identified by PCR as D5, a member of the D1-like dopamine receptor subfamily, and D4, a member of the D2-like dopamine receptor subfamily. The purpose of this study was to determine whether activation of D5 or D4 receptors inhibits influx of Na+, which could explain inhibition of secretion and Ca2+ uptake by dopamine agonists. D1-selective agonists preferentially inhibited both dimethylphenylpiperazinium- (DMPP) and veratridine-stimulated 22Na+ influx into chromaffin cells. The D1-selective agonists chloro-APB hydrobromide (Cl- APB; 100 μM) and SKF-38393 (100 μM) inhibited DMPP-stimulated Na+ uptake by 87.5 ± 2.3 and 59.7 ± 4.5%, respectively, whereas the D2-selective agonist bromocriptine (100 μM) inhibited Na+ uptake by only 22.9 ± 5.0%. Veratridine-stimulated Na+ uptake was inhibited 95.1 ± 3.2 and 25.7 ± 4.7% by 100 μM Cl-APB or bromocriptine, respectively. The effect of Cl-APB was concentration dependent. A similar IC50 (~18 μM) for inhibition of both DMPP- and veratridine-stimulated Na+ uptake was obtained. The addition of 8- bromo-cyclic AMP (1 mM) had no effect on either DMPP- or veratridine- stimulated Na+ uptake. These observations suggest that D1-selective agonists are inhibiting secretagogue-stimulated Na+ uptake in a cyclic AMP- independent manner.

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