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 microM) and SKF-38393 (< 00 microM) inhibited DMPP-stimulated Na+ uptake by 87.5 +/- 2.3 and 59.7 +/- 4.5%, respectively, whereas the D2-selective agonist bromocriptine (100 microM) 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 microM CI-APB or bromocriptine, respectively. The effect of CI-APB was concentration dependent. A similar IC50 (approximately 18 microM) 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.
Dahmer
M K
MK
Department of Biochemistry, College of Medicine, University of Tennessee, Memphis 38163, USA.
Senogles
S E
SE
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D007700:Kinetics; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D012964:Sodium / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D005576:Colforsin; D001971:Bromocriptine; D013779:Tetrodotoxin; D004246:Dimethylphenylpiperazinium Iodide; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D014701:Veratridine; C071262:SK&F 82958; D012964:Sodium