Binding of the bidentate inhibitor [3H]HACBO-Gly to the rat brain neutral endopeptidase “enkephalinase”
1985; Elsevier BV; Volume: 131; Issue: 1 Linguagem: Inglês
10.1016/0006-291x(85)91797-8
ISSN1090-2104
AutoresGilles Waksman, Romaine Bouboutou, Jocelyne Devin, R. Besselièvre, Marie‐Claude Fournié‐Zaluski, Bernárd P. Roques,
Tópico(s)Diabetes Treatment and Management
ResumoThe 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.
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