Effect of repetitive icv injections of ANG II on c-Fos and AT1-receptor expression in the rat brain

被引:48
作者
Moellenhoff, E
Blume, A
Culman, J
Chatterjee, B
Herdegen, T
Lebrun, CJ
Unger, T
机构
[1] Univ Kiel, Inst Pharmacol, D-24105 Kiel, Germany
[2] German Inst High Blood Pressure Res, D-69120 Heidelberg, Germany
[3] Gesselschaft Strahlenforsch, Natl Res Ctr Environm & Hlth, Inst Mammalian Genet, D-85764 Neuherberg, Germany
关键词
chronic stimulation; desensitization; inducible transcription factor; constitutive transcription factor; angiotensin AT(1); receptor; intracerebroventricular;
D O I
10.1152/ajpregu.2001.280.4.R1095
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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 AT(1) 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 similar to 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 AT(1) receptor was coexpressed with c-Fos/c-Jun. Immunohistochemical stainings suggest an increase in AT(1) 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 AT(1) receptor transcription.
引用
收藏
页码:R1095 / R1104
页数:10
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