Localization of central angiotensin II receptors with [125I]-sar1, ile8-angiotensin II: periventricular sites of the anterior third ventricle.
The radiolabeled angiotensin II (ANG II) antagonist, [N 125I]-sar1,ile8-ANG II, was used to study brain ANG II receptors by both homogenate binding and in vitro autoradiography. In homogenate preparations of the hypothalamus, thalamus, septum and midbrain (HTSM), [125I]-sar1,ile8-ANG II bound to a single class (Hill slope 0.84 +/- 0.05) of high affinity binding sites (KD 0.42 +/- 0.03 nM, Bmax 5.98 +/- fmol/mg protein). Competition for the [125I]-sar1,ile8-ANG II binding site in HTSM membranes demonstrated a rank order potency characteristic of binding to the ANG II receptor, with the unlabeled antagonist being slightly more potent than ANG II (Ki 0.22 +/- 0.03 vs 0.95 +/- 0.06 nM, respectively). Brain slices from the region of the rostral third ventricle were incubated with 0.5 nM[125I]-sar1,ile8-ANG II in the presence or absence of 1 microM ANG II and exposed to LKB Ultrofilm. Autoradiographic images of [125I]-sar1,ile8-ANG II binding revealed that structures situated within the anterior wall of the third ventricle, i.e. the lamina terminalis, were heavily labeled; including the subfornical organ, median preoptic nucleus and organum vasculosum laminae terminalis. These results show the utility of [125I]-sar1,ile8-ANG II as a probe to study brain ANG II receptors and provides pharmacological evidence for the rostral third ventricle as a possible site for central ANG II actions.
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002552:Cerebral Ventricles / Q000378:metabolism*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000032:analysis / Q000378:metabolism*
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D015059:1-Sarcosine-8-Isoleucine Angiotensin II