Changes in angiotensin II receptor 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 do paminergic nerve terminal-rich brain regions (caudate putamen, nucleus accu mbens, 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 week s (old). The receptors were labeled with I-125-sarcosine(1), isoleucine(8) angiotensin II (I-125-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 AT(1) receptor subtype antagonist PD 123319 (10 mu M) was used to inhibit I-125-SI Ang II binding to AT(1) receptors to determine AT(1) receptor density in brain sections. In young control mice the density of Ang II receptor binding sites in the c audate 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 I-125-SI Ang II binding was displaced b y PD 123319, suggesting that nearly all of the Ang II receptors in these br ain regions were the AT(1) subtype. The B-max in homogenates of these three regions in young control mice was 11.0 +/- 2.1 fmol/mg protein. The K-D wa s 0.49 +/- 0.13. Ang II receptors in old mouse brains were decreased, respe ctively, by 32%, 35% and 30% in the caudate putamen, nucleus accumbens and ventral pallidum (p < 0.001). Ang II receptors were slightly, but not signi ficantly increased in both young and old EtOH-consuming mice. (C) 1999 Else vier Science B.V. All rights reserved.