Central angiotensin AT1 and muscarinic receptors in ITF expression on intracerebroventricular NaCl.
In the present study, we investigated the expression pattern of the inducible transcription factors (ITF) c-Fos, c-Jun, JunB, JunD, and Krox-24 following intracerebroventricular injections of hyperosmolar saline (0.2, 0.3, and 0.6 M NaCl) and its mediation via angiotensin and/or muscarinic receptors. c-Fos, c-Jun, and Krox-24 were differentially expressed in organum vasculosum laminae terminalis, median preoptic area, subfornical organ (SFO), and paraventricular and supraoptic nuclei. Expression of c-Fos and c-Jun was inhibited by pretreatment with the angiotensin AT1 receptor antagonist losartan (10 and 20 nmol icv) following 0.20 and 0.30 M saline. Pretreatment with atropine (15 nmol icv) inhibited the 0.30 and 0.60 M NaCl-induced expression of c-Fos, c-Jun, and Krox-24 in all areas except the SFO. Coexpression of the ITF with vasopressin and oxytocin, the major effector peptides in osmoregulation, was demonstrated, implying the corresponding genes as putative target genes of the ITF. The results show a highly differentiated ITF expression pattern in the brain mediated by angiotensinergic and muscarinergic pathways, suggesting a finely tuned regulation of target genes.
Institute of Pharmacology, University of Kiel, 24105 Kiel; and German Institute for High Blood Pressure Research, 69120 Heidelberg, Germany.
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Moellenhoff
C J
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Lebrun
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Blume
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Culman
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Herdegen
T
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Unger
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002552:Cerebral Ventricles / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D017874:Immediate-Early Proteins; D007276:Injections, Intraventricular; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D010121:Oxytocin / Q000096:biosynthesis; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D011301:Preoptic Area / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000494:pharmacology*; D013495:Supraoptic Nucleus / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis*; D014667:Vasopressins / Q000096:biosynthesis; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011945:Receptors, Angiotensin; D011976:Receptors, Muscarinic; D012462:Saline Solution, Hypertonic; D014157:Transcription Factors; D014667:Vasopressins; D010121:Oxytocin; D001285:Atropine; D019808:Losartan