Expression of aldosterone synthase cytochrome P450 (P450aldo) mRNA in rat adrenal glomerulosa cells by angiotensin II type 1 receptor.
Changes in the mRNA levels for aldosterone synthase cytochrome P450 (P450aldo or CYP11B2) in rat adrenal glands were studied in response to angiotensin II type 1 (AT1) and type 2 (AT2) receptor antagonists. Since 11 beta hydroxylase P450 (P45011 beta or CYP11B1), which shows high homology (88.5%) with P450aldo in their nucleotide sequences of the amino acid coding regions, is also expressed in the adrenal gland, RT-PCR was performed with specific primers for each P450. Upon sodium restriction (5 mmol Na+/kg of diet) of the rats for 14 days, the amount of the P450aldo mRNA in the adrenal glands increased 8.5 fold above from the rats fed on a normal diet (225 mmol Na+/kg of diet), whereas no significant change of the P45011 beta mRNA was observed after the dietary sodium restriction. As shown by an immunoblot analysis, the adrenal capsule portions (mainly zona glomerulosa) of the rats kept on the low Na diet for 14 days expressed significantly higher level of P450aldo than those from the rats fed the normal diet. In concert with the alteration, plasma aldosterone concentration increased. However, when a specific AT1 antagonist E4177 was given to the rats kept on a low Na diet, the amount and activity of P450aldo as well as the plasma aldosterone concentration was suppressed. On the other hand, the increase of P450aldo induced by the low Na diet was not affected by an AT2-specific antagonist, PD123177.
Kakiki
M
M
Department of Drug Metabolism Research, Eisai Tsukuba Research Laboratories, Ibaraki, Japan.
Morohashi
K
K
Nomura
M
M
Omura
T
T
Horie
T
T
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D019405:Cytochrome P-450 CYP11B2 / Q000187:drug effects* / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D016133:Polymerase Chain Reaction; D011725:Pyridines / Q000494:pharmacology*; D012313:RNA / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood / Q000187:drug effects; D012982:Sodium, Dietary / Q000494:pharmacology; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D015384:Zona Glomerulosa / Q000166:cytology / Q000201:enzymology*
D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D012982:Sodium, Dietary; D000804:Angiotensin II; C066253:PD 123177; C083778:3-((2'-carboxybiphenyl-4-yl)methyl)-2-cyclopropyl-7-methyl-3H-imidazo(4,5-b)pyridine; D000450:Aldosterone; D012313:RNA; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D012083:Renin