Changes in angiotensin II receptors in dopamine-rich regions of the mouse brain with age and ethanol consumption.
The density of angiotensin II (Ang II) receptors was determined in three dopaminergic nerve terminal-rich brain regions (caudate putamen, nucleus accumbens, and ventral pallidum) of mice that were given either water (control) or 20% w/v ethanol (EtOH) to drink for either 2-8 weeks (young) or 46 weeks (old). The receptors were labeled with 125I-sarcosine1, isoleucine8 angiotensin II (125I-SI Ang II) and measured by quantitative densitometric image analysis (receptor autoradiography) or by saturation binding assays on homogenates of these brain regions. The selective AT2 receptor subtype antagonist PD 123319 (10 microM) was used to inhibit 125I-SI Ang II binding to AT2 receptors to determine AT1 receptor density in brain sections. In young control mice the density of Ang II receptor binding sites in the caudate putamen was 407+/-26 fmol/g, in the nucleus accumbens the density was 346+/-27 fmol/g, and in the ventral pallidum the density was 317+/-27 fmol/g. Less than 5% of specific 125I-SI Ang II binding was displaced by PD 123319, suggesting that nearly all of the Ang II receptors in these brain regions were the AT1 subtype. The Bmax in homogenates of these three regions in young control mice was 11.0+/-2.1 fmol/mg protein. The KD was 0.49+/-0.13. Ang II receptors in old mouse brains were decreased, respectively, by 32%, 35% and 30% in the caudate putamen, nucleus accumbens and ventral pallidum (p<0.001). Ang II receptors were slightly, but not significantly increased in both young and old EtOH-consuming mice.
Daubert
D L
DL
Program in Neuroscience, Washington State University, Pullman, WA 99164-6520, USA.
Meadows
G G
GG
Wang
J H
JH
Sanchez
P J
PJ
Speth
R C
RC
D000375:Aging; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005917:Globus Pallidus / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism; D007457:Iodine Radioisotopes; D051379:Mice; D008810:Mice, Inbred C57BL; D009714:Nucleus Accumbens / Q000378:metabolism; D011485:Protein Binding; D011699:Putamen / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism*
D007093:Imidazoles; D007457:Iodine Radioisotopes; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C073402:PD 123319; D000431:Ethanol; D004298:Dopamine