[125I]CGP 42112 reveals a non-angiotensin II binding site in 1-methyl-4-phenylpyridine (MPP+)-induced brain injury.
1. Intracerebral injection of the oxidative metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridine (MPP+), into the substantia nigra of adult rats resulted in a lesion at the injection site. 2. Using autoradiography, we localized specific [125I]CGP 42112 binding that was not recognized by angiotensin II or angiotensin II AT1 or AT2 receptor-selective ligands. 3. Our results suggest that [125I]CGP 42112 may be binding to activated microglia that appear at the lesion site.
Viswanathan
M
M
Section on Pharmacology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892.
de Oliveira
A M
AM
Wu
R M
RM
Chiueh
C C
CC
Saavedra
J M
JM
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001713:Biphenyl Compounds / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007457:Iodine Radioisotopes; D019808:Losartan; D008297:Male; D009842:Oligopeptides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D007457:Iodine Radioisotopes; D009842:Oligopeptides; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C060894:CGP 42112A; D019808:Losartan; D015655:1-Methyl-4-phenylpyridinium