Differential Inhibition of Secretagogue‐Stimulated Sodium Uptake in Adrenal Chromaffin Cells by Activation of D4 and D5 Dopamine Receptors

: 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 (CI‐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 CI‐APB or bromocriptine, respectively. The effect of CI‐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.