Binding of the bidentate inhibitor [3H]HACBO-Gly to the rat brain neutral endopeptidase "enkephalinase".
The synthesis and binding properties to rat brain tissue of the enkephalinase inhibitor [3H] N-[(R,S)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl]-glycine ([3H]HACBO-Gly, 45 Ci/mmole) is reported. [3H]HACBO-Gly binding to membranes from various rat brain tissue is saturable (KD = 0.4 +/- 0.05 nM) and linearly related to the amount of tissue. Non specific binding is less than 15% of total binding at the KD concentration. The regional distribution of [3H]HACBO-Gly binding and enkephalinase activity are closely correlated with highest levels in striatum and substantia nigra. The efficiency of inhibitors of various peptidases (thiorphan, captopril, bestatin ...) to inhibit [3H]HACBO-Gly binding or enkephalinase activity are similar. These results indicate that [3H]HACBO-Gly binds selectively to enkephalinase. This compound should help to clarify the localization of the enzyme in the CNS.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002216:Captopril / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D003342:Corpus Striatum / Q000201:enzymology; D005998:Glycine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006898:Hydroxylamines / Q000378:metabolism* / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D015260:Neprilysin; D011480:Protease Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000201:enzymology; D015244:Thiorphan; D008625:Tiopronin / Q000031:analogs & derivatives / Q000494:pharmacology; D014018:Tissue Distribution
D006898:Hydroxylamines; D011480:Protease Inhibitors; C046556:N-(3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl)glycine; D002216:Captopril; D015244:Thiorphan; D008625:Tiopronin; D015260:Neprilysin; D007930:Leucine; C012211:ubenimex; D005998:Glycine