[H-3]IVDE77, a novel radioligand with high affinity and selectivity for the insulin-regulated aminopeptidase
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Tartalom: http://real.mtak.hu/7319/
Archívum: REAL
Gyűjtemény: Status = Published
Subject = Q Science / természettudomány: QH Natural history / természetrajz: QH301 Biology / biológia: QH3011 Biochemistry / biokémia
Subject = Q Science / természettudomány: QH Natural history / természetrajz: QH301 Biology / biológia
Subject = R Medicine / orvostudomány: RM Therapeutics. Pharmacology / terápia, gyógyszertan
Type = Article
Cím:
[H-3]IVDE77, a novel radioligand with high affinity and selectivity for the insulin-regulated aminopeptidase
Létrehozó:
Nikolaou, Alexandros
Van Den Eynde, Isabelle
Tourwé, Dirk
Vauquelin, Georges
Tóth, Géza
Mallareddy, Jayapal Reddy
Vanderheyden, Patrick M. L.
Dátum:
2013
Téma:
QH301 Biology / biológia
QH3011 Biochemistry / biokémia
RM Therapeutics. Pharmacology / terápia, gyógyszertan
Tartalmi leírás:
The hexapeptide angiotensin IV (Ang IV) induces diverse biological effects such as memory enhancement and protection against ischemic stroke. Studies on the mechanism of Ang IV however are hampered by its instability and its lack of selectivity. The high-affinity binding site for Ang IV is the insulin-regulated aminopeptidase (IRAP, EC 3.4.11.3), but Mg IV also acts as a weak agonist for the Ang II-receptor (AT(1)), implying the need for stable and highly selective Mg IV-analogues. Here we present the screening of novel Mg IV-analogues, selected on basis of high affinity for IRAP, high selectivity (compared to aminopeptidase N and the AT(1), receptor) and resistance against proteases. The selected compound IVDE77 possesses a number of advantages compared to Ang IV: (i) it has a 40 times higher affinity for IRAP (K-i 1.71 nM), (ii) it does not activate the AT(1), receptor, (iii) it is easily radiolabeled with tritium and (iv) it is resistant to proteolysis, even in human plasma. In addition, pre-treatment of intact CHO-K1 cells with IVDE77 led to a virtually complete inhibition of subsequent intracellular accumulation of [H-3]IVDE77-IRAP complexes. IVDE77 thus represents the first Ang IV-analogue able to abolish IRAP-availability completely at the cell surface in vitro. In summary, IVDE77 is a useful tool for the detection of IRAP under physiological conditions, and may contribute to elucidating the mechanism of Ang IV to ascertain which functions are IRAP-dependent. (C) 2013 Elsevier B.V. All rights reserved.
Típus:
Article
PeerReviewed
Formátum:
text
Azonosító:
Nikolaou, Alexandros and Van Den Eynde, Isabelle and Tourwé, Dirk and Vauquelin, Georges and Tóth, Géza and Mallareddy, Jayapal Reddy and Vanderheyden, Patrick M. L. (2013) [H-3]IVDE77, a novel radioligand with high affinity and selectivity for the insulin-regulated aminopeptidase. EUROPEAN JOURNAL OF PHARMACOLOGY, 702 (1-3). pp. 93-102. ISSN 0014-2999
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