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Differential Inhibition of Secretagogue‐Stimulated Sodium Uptake in Adrenal Chromaffin Cells by Activation of D4 and D5 Dopamine Receptors
Author(s) -
Dahmer Mary K.,
Senogles Susan E.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67051960.x
Subject(s) - veratridine , secretagogue , medicine , endocrinology , chemistry , quinpirole , dopamine , agonist , receptor , chromaffin cell , adrenal medulla , dopamine receptor , dopamine receptor d2 , muscarine , catecholamine , sodium , sodium channel , biology , biochemistry , muscarinic acetylcholine receptor , organic chemistry
Recent studies have demonstrated that D1‐selective and D2‐selective dopamine receptor agonists inhibit catecholamine secretion and Ca 2+ 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 Ca 2+ uptake by dopamine agonists. D1‐selective agonists preferentially inhibited both dimethylphenylpiperazinium‐ (DMPP) and veratridine‐stimulated 22 Na + influx into chromaffin cells. The D1‐selective agonists chloro‐APB hydrobromide (CI‐APB; 100 µ M ) and SKF‐38393 (100 µ M ) inhibited DMPP‐stimulated Na + uptake by 87.5 ± 2.3 and 59.7 ± 4.5%, respectively, whereas the D2‐selective agonist bromocriptine (100 µ M ) 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 µ M CI‐APB or bromocriptine, respectively. The effect of CI‐APB was concentration dependent. A similar IC 50 (∼18 µ M ) for inhibition of both DMPP‐ and veratridine‐stimulated Na + uptake was obtained. The addition of 8‐bromo‐cyclic AMP (1 m M ) 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.