Effect of repetitive icv injections of ANG II on c-Fos and AT(1)-receptor expression in the rat brain.
ANG II has been implicated in neuroplastic processes via stimulation of inducible transcription factors (ITF) in the brain. In the present study, we investigated the effects of acute vs. repetitive once daily intracerebroventricular injections of ANG II for 7 days on the expression of ITF and constitutive transcription factor (CTF) and the AT1 receptor in the median preoptic area (MnPO), the subfornical organ (SFO), and the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON). After repetitive injections, the expression of c-Fos declined by approximately 50% in MnPO, SFO, PVN, and SON compared with controls injected once. The desensitization of c-Fos occurred on the transcriptional level as shown in the SON by RT-PCR. Apart from a novel expression of c-Jun in the SON, the ITF c-Jun, JunB, JunD, and Krox-24 did not change after repetitive stimulation. Neither were the CTF, calcium response element binding protein, activating transcription factor 2, and serum response factor altered after repetitive vs. single injections of ANG II. The AT1 receptor was coexpressed with c-Fos/c-Jun. Immunohistochemical stainings suggest an increase in AT1-receptor number in MnPO, SFO, PVN, and SON on chronic stimulation compared with once-injected controls. These findings demonstrate that repetitive periventricular stimulation with ANG II essentially alters the expression of transcription factors compared with acute stimulation and suggest c-Fos and c-Jun as major intermediates of the AT1-receptor transcription.
Institute of Pharmacology, University of Kiel, Hospitalstrasse 4, 24105 Kiel, Germany.
E
E
Moellenhoff
A
A
Blume
J
J
Culman
B
B
Chatterjee
T
T
Herdegen
C J
CJ
Lebrun
T
T
Unger
D051698:Activating Transcription Factor 2; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D004334:Drug Administration Schedule; D016762:Genes, fos / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology; D011301:Preoptic Area / Q000187:drug effects / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026362:Serum Response Factor; D013356:Subfornical Organ / Q000187:drug effects / Q000502:physiology; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D051698:Activating Transcription Factor 2; C497107:Atf2 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D026362:Serum Response Factor; D014157:Transcription Factors; C064360:crb protein, Drosophila; D000804:Angiotensin II