The role of calcium channels in hamster CYP11B2 gene expression

Previous studies have shown that the hamster CYP11B2 gene promoter is under the influence of angiotensin II (AII), cAMP and potassium (K+). However, very little is known about the mechanisms by which these compounds regulate the transcription of the CYP11B2 gene. Therefore we analysed the 5'-flanking region of the hamster CYP11B2 gene using a transient transfection expression system in NCI-H295 adrenocortical cells, which are known to respond to K+, cAMP and AII. The first 486 bp before the transcription initiation site were introduced upstream of the chloramphenicol acetyl transferase gene. NCI-H295 cells transfected with this -486 construct showed increased CAT activity upon treatment by K+, AII, forskolin and cAMP. The calcium channel antagonist nifedipine partially blocked the enhancing effects of AII, forskolin and cAMP by 35%, 30% and 30% respectively, whereas it completely blocked the stimulatory effects of KCl (1). These results thus show the involvement of calcium channels in the regulation of CYP11B2 gene transcription by K+, and their partial involvement in the regulation of this gene by AII, forskolin and cAMP in NCI-H295 cells.