PMID- 8584752
OWN - NLM
STAT- MEDLINE
DCOM- 19960315
LR  - 20190830
IS  - 0167-0115 (Print)
IS  - 0167-0115 (Linking)
VI  - 59
IP  - 2
DP  - 1995 Oct 20
TI  - A decrease in angiotensin receptor binding in rat brain nuclei by antisense 
      oligonucleotides to the angiotensin AT1 receptor.
PG  - 171-82
AB  - Intracerebroventricular (i.c.v.) injections of antisense oligonucleotides against 
      mRNA of the angiotensin type 1 (AT1) receptor have been shown to reduce blood 
      pressure in spontaneously hypertensive (SHR) rats and angiotensin II-induced 
      drinking in both SHR and Sprague-Dawley (SD) rats. The present investigation was 
      designed to quantify the effect of i.c.v. injections of antisense 
      oligonucleotides to the AT1 receptor mRNA on brain angiotensin receptors using 
      membrane binding and autoradiographic analysis. Control injections contained 
      sense or scrambled oligonucleotides or saline. Three daily injections of 
      antisense oligonucleotides into the third ventricle of SD rats decreased the AT1 
      receptor number significantly by 25% in a hypothalamic tissue block. AT2 
      receptors were not altered. Autoradiography showed a decrease in angiotensin 
      receptor number in hypothalamic nuclei and in the anteroventral region of the 
      third ventricle (AV3V) after antisense treatment. AT2 receptors were not reduced 
      indicating the AT1 antisense oligonucleotides were specific. In a second series 
      of experiments, single injections of antisense oligonucleotides into the lateral 
      ventricle of SHR rats were tested. Antisense oligonucleotides produced a 
      significant decrease in receptor number in the same hypothalamic area. Sense and 
      scrambled oligonucleotides did not decrease the receptor numbers significantly. 
      The decreases observed after injection of antisense oligonucleotides were between 
      15 and 30%. These changes may be sufficient to account for the physiological 
      effects of i.c.v. injections of antisense oligonucleotides to AT1 receptor mRNA.
FAU - Ambuhl, P
AU  - Ambuhl P
AD  - University of Florida, College of Medicine, Department of Physiology, Gainesville 
      32610, USA.
FAU - Gyurko, R
AU  - Gyurko R
FAU - Phillips, M I
AU  - Phillips MI
LA  - eng
GR  - HL27334/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Regul Pept
JT  - Regulatory peptides
JID - 8100479
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Receptors, Angiotensin)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Autoradiography
MH  - Cerebral Ventricles/*drug effects/metabolism
MH  - Hypertension/*metabolism
MH  - Injections, Intraventricular
MH  - Male
MH  - Oligonucleotides, Antisense/metabolism/*pharmacology
MH  - Paraventricular Hypothalamic Nucleus/*drug effects/metabolism
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Sprague-Dawley
MH  - Receptors, Angiotensin/*drug effects/metabolism
EDAT- 1995/10/20 00:00
MHDA- 1995/10/20 00:01
CRDT- 1995/10/20 00:00
PHST- 1995/10/20 00:00 [pubmed]
PHST- 1995/10/20 00:01 [medline]
PHST- 1995/10/20 00:00 [entrez]
AID - 016701159500092P [pii]
AID - 10.1016/0167-0115(95)00092-p [doi]
PST - ppublish
SO  - Regul Pept. 1995 Oct 20;59(2):171-82. doi: 10.1016/0167-0115(95)00092-p.