Access of peripherally administered DuP 753 to rat brain angiotensin II receptors.
The in vivo access of the nonpeptide angiotensin II (Ang II) antagonist, DuP 753 (10 mg kg-1, i.v.), to Ang II receptors of rat brain was investigated by in vitro autoradiography with [125I]-[Sar1, Ile8] Ang II as a ligand. DuP 753 markedly inhibited the binding to sites which contain exclusively AT1 receptors both outside and within the blood brain barrier, such as the circumventricular organs, paraventricular hypothalamic nucleus, median preoptic nucleus and nucleus of the solitary tract. However, binding to other nuclei containing AT2 receptors was not significantly inhibited. These results demonstrate that DuP 753 and/or its active metabolite readily cross the blood brain barrier in vivo and selectively inhibit binding to AT1 receptors in specific brain nuclei.
Song
K F
KF
Department of Medicine, Austin Hospital, University of Melbourne, Heidelberg, Victoria, Australia.
Zhuo
J L
JL
Mendelsohn
F A
FA
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001345:Autoradiography; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D019808:Losartan; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D007457:Iodine Radioisotopes; D013777:Tetrazoles; D000804:Angiotensin II; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D019808:Losartan