Nuclear angiotensin receptors induce transcription of renin and angiotensinogen mRNA.
The observation that nuclei from hepatic tissue exhibit specific angiotensin II (Ang II) binding led us to explore whether Ang II modulates mRNA in general, mRNA specific for renin system components, or both. Nuclei from hepatic tissue exhibited a single high-affinity (Kd = 0.4 nmol/L) Ang II-specific binding site, which was associated with increased RNA transcription. Whereas total RNA extracted from nuclei increased 1.5-fold in response to Ang II (10(-9) mol/L), specific mRNA for renin and angiotensinogen increased 7.8- and 2.5-fold, respectively. Ang II binding and induced transcription showed parallel Ang II dose responses that were both inhibited by 10(-5) mol/L DuP 753 or saralasin. Maximum Ang II binding and RNA transcription occurred at the same Ang II concentration (10(-9) mol/L). Higher doses of Ang II resulted in a progressive decrease in RNA transcription. Together, these results demonstrate that hepatic nuclei have functional Ang II-specific receptors. It is concluded that Ang II may elicit responses at nuclear receptors, which heretofore were associated only with Ang II receptors located on plasma membranes. However, the individual contribution of plasma and nuclear membrane Ang II receptors to the overall cellular Ang II transcriptional response and their possible interactions remain to be determined.
Eggena
P
P
Renin Biochemistry/Vascular Pharmacology Laboratories, Department of Veterans Affairs Medical Center, Sepulveda, CA 91343.
Zhu
J H
JH
Clegg
K
K
Barrett
J D
JD
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology*; D012083:Renin / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D000804:Angiotensin II; D012083:Renin