Dopamine selectively inhibits angiotensin II-induced aldosterone secretion by interacting with D-2 receptors.
Aldosterone secretion is subject to both stimulatory and inhibitory controls. Angiotensin II (AII) is the primary stimulator of aldosterone production and an inhibitory role of dopamine (DA) has been suggested recently. In this study we investigated the interactions between DA and AII in the intracellular events leading to aldosterone secretion. By measuring aldosterone secretion and cyclic AMP (cAMP) formation in intact adrenal glomerulosa cells we show that AII induced a sustained stimulation of aldosterone secretion (EC50, 0.41 nM) and a rapid and transient increase in intracellular cAMP content (EC50, 4 nM). DA inhibited both aldosterone secretion (IC50, 300 nM) and cAMP formation (IC50, 100 nM) elicited by submaximal concentrations of AII; in contrast, DA did not attenuate either basal or adrenocorticotropic hormone-stimulated cell activity. The pharmacological characterization of DA effects with dopaminergic agonists and antagonists strongly indicated an involvement of D-2 receptors. Indeed, selective D-2 agonists were more effective than DA in inhibiting the glomerulosa cell responses to AII; in addition, the effects of DA on both aldosterone secretion and cAMP formation were prevented by D-2 antagonists, such as (-)-sulpiride and domperidone, but not by the selective D-1 antagonist SCH 23390. These data suggest a specific functional interaction between D-2 receptors apparently associated with inhibition of cAMP formation and AII in the regulation of aldosterone production.
Missale
C
C
Institute of Pharmacology and Experimental Therapeutics, School of Medicine, University of Brescia, Italy.
Memo
M
M
Liberini
P
P
Spano
P
P
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001971:Bromocriptine / Q000494:pharmacology; D002069:Butaclamol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*
D001552:Benzazepines; D011954:Receptors, Dopamine; D000804:Angiotensin II; D001971:Bromocriptine; D000450:Aldosterone; D002069:Butaclamol; D000242:Cyclic AMP; D006220:Haloperidol; D004298:Dopamine