Inhibition of the expression of the gene for the angiotensin AT1 receptor by angiotensin II in the rat adrenal gland.
The expression of angiotensin AT1A and AT1B receptor mRNA after continuous angiotensin II administration was investigated in the rat adrenal gland. Angiotensin AT1 receptor mRNA detected by Northern blot analysis decreased to 52.7+/-16.1% of control after the administration of angiotensin II (20 microg/h) for 24 h, and to 70.8+/-8.0% after 1 week. A low dose of angiotensin II (0.2 microg/h) also decreased angiotensin AT1 receptor mRNA to 73.0+/-5.5% after 1 week. Competitive reverse transcription and polymerase chain reaction (RT-PCR) experiments revealed that both angiotensin AT1A and AT1B receptor mRNAs decreased after administration of angiotensin II (20 or 0.2 microg/h) for 1 week. Analysis of the angiotensin AT1A promoter by using luciferase-reporter system showed that angiotensin II (up to 1 microM) did not have any effects on the promoter activity (106+/-5.7% after 0.1 microM angiotensin II stimulation) in Y1 cells and cultured vascular smooth muscle cells, although phorbol myristate acetate (PMA) decreased the promoter activity by about 40% compared with control. These results suggest that angiotensin AT1 receptor gene expression in the rat adrenal gland is inhibited by angiotensin II and it may not be due to suppression of promoter activity. Other mechanisms such as destabilization of angiotensin AT1 receptor mRNA or angiotensin II-induced increased blood pressure may be involved in the inhibition.
Ishihata
A
A
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA. ishihata@med.id.yamagata-u.ac.jp
Uno
S
S
Guo
D F
DF
Katano
Y
Y
Inagami
T
T
D000311:Adrenal Glands / Q000502:physiology*; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure; D005786:Gene Expression Regulation; D006339:Heart Rate; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II