Down-Regulation of D2 Dopamine Receptor and Increased Protein Kinase Cμ Phosphorylation in Aldosterone-Producing Adenoma Play Roles in Aldosterone Overproduction

Context: The mechanism associated with the overproduction of aldosterone by aldosterone-producing adenomas (APA) is unknown. Objective: The objective of the study was to explore the role of the D2 dopamine receptor (D2R) on aldosterone synthesis and secretion and clarify the clinical importance of this role on aldosterone overproduction in APA. Results: D2R expression in APA was examined in 24 patients and was much less than that in the nontumorous adrenal cortex. D2R mRNA levels in APA were inversely correlated with CYP11B2 mRNA levels and the patient’s plasma aldosterone concentration. Angiotensin II (AII)-stimulated aldosterone secretion and CYP11B2 mRNA expression in human adrenocarcinoma cells (H295R) was attenuated by the D2 agonist, bromocriptine (BMC). BMC selectively attenuated AII-induced protein kinase C (PKC)-μ phosphorylation and its translocation to the cell membrane. PKCμ-specific short-hairpin RNA significantly decreased AII-induced CYP11B2 mRNA expression and aldosterone secretion. BMC al...