TY  - JOUR
AU  - Demaegdt, H
AU  - De Backer, JP
AU  - Lukaszuk, A
AU  - Tóth, Géza
AU  - Szemenyei, Erzsébet
AU  - Tourwe, D
AU  - Vauquelin, G
TI  - Angiotensin IV displays only low affinity for native insulin-regulated aminopeptidase (IRAP).
JF  - FUNDAMENTAL & CLINICAL PHARMACOLOGY
J2  - FUND CLIN PHARMACOL
VL  - 26
PY  - 2012
IS  - 2
SP  - 194
EP  - 197
PG  - 4
SN  - 0767-3981
DO  - 10.1111/j.1472-8206.2011.00948.x
UR  - https://m2.mtmt.hu/api/publication/1921994
ID  - 1921994
AB  - Radioligand binding studies revealed that Ang IV binds to insulin-regulated aminopeptidase (IRAP)/'AT(4) receptors' with high affinity. Yet, as these experiments were routinely carried out in the presence of chelators, only the catalytic zinc-depleted apo-form of IRAP was labelled. While the chelators remove the catalytic zinc from IRAP and protect Ang IV from proteolytic degradation, the aminopeptidase N selective inhibitor '7B' only exerts the latter effect. By using 7B along with the new stable Ang IV-analog [(3) H]AL-11, we here show that the native enzyme is only a low-affinity target for Ang IV.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Demaegdt, Heidi
AU  - Gard, Paul
AU  - De Backer, Jean-Paul
AU  - Lukaszuk, Aneta
AU  - Szemenyei, Erzsébet
AU  - Tóth, Géza
AU  - Tourwe, Dirk
AU  - Vauquelin, Georges
TI  - Binding of "AT(4) receptor" ligands to insulin regulated aminopeptidase (IRAP) in intact Chinese hamster ovary cells
JF  - MOLECULAR AND CELLULAR ENDOCRINOLOGY
J2  - MOL CELL ENDOCRINOL
VL  - 339
PY  - 2011
IS  - 1-2
SP  - 34
EP  - 44
PG  - 11
SN  - 0303-7207
DO  - 10.1016/j.mce.2011.03.005
UR  - https://m2.mtmt.hu/api/publication/1921802
ID  - 1921802
N1  - Megjegyzés-22145408
DI: 10.1016/j.mce.2011.03.005
Megjegyzés-22214366
DI: 10.1016/j.mce.2011.03.005
Megjegyzés-22217248
DI: 10.1016/j.mce.2011.03.005
Megjegyzés-22226938
DI: 10.1016/j.mce.2011.03.005
AB  - Insulin regulated aminopeptidase (IRAP) recognises "AT(4)-receptor" ligands like angiotensin IV (Ang IV) and peptidomimetics like AL-11. The metabolic stability and high affinity of [(3)H]AL-11 for catalytically active IRAP allowed its detection in Chinese hamster ovary (CHO-K1) cell membranes in the absence of chelators (Demaegdt et al., 2009). Here, we show that, contrary to [(3)H]Ang IV, [(3)H]AL-11 displays high affinity and specificity for IRAP in intact CHO-K1 cells as well. After binding to IRAP at the surface, [(3)H]AL-11 is effectively internalized by an endocytotic process. Unexpectedly, surface binding and internalization of [(3)H]AL-11 was not affected by pretreating the cells with Ang IV but declined with AL-11. In the latter case surface expression of IRAP even increased. After elimination of simpler explanations, it is proposed that metabolically stable "AT(4)-receptor" ligands undergo semi-continuous cycling between the cell surface and endosomal compartments. The in vivo efficacy of stable and unstable "AT4-receptor" ligands could therefore differ. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Demaegdt, H
AU  - Lukaszuk, A
AU  - De Buyser, E
AU  - De Backer, JP
AU  - Szemenyei, Erzsébet
AU  - Tóth, Géza
AU  - Chakravarthy, S
AU  - Panicker, M
AU  - Michotte, Y
AU  - Tourwe, D
AU  - Vauquelin, G
TI  - Selective labeling of irap by the tritiated at(4) receptor ligand [h-3]angiotensin iv and its stable analog [h-3]al-11
JF  - MOLECULAR AND CELLULAR ENDOCRINOLOGY
J2  - MOL CELL ENDOCRINOL
VL  - 311
PY  - 2009
IS  - 1-2
SP  - 77
EP  - 86
PG  - 10
SN  - 0303-7207
DO  - 10.1016/j.mce.2009.07.020
UR  - https://m2.mtmt.hu/api/publication/1920919
ID  - 1920919
N1  - Megjegyzés-22145410
DI: 10.1016/j.mce.2009.07.020
Megjegyzés-22214373
DI: 10.1016/j.mce.2009.07.020
Megjegyzés-22217251
DI: 10.1016/j.mce.2009.07.020
LA  - English
DB  - MTMT
ER  - 

TY  - THES
AU  - Szemenyei, Erzsébet
TI  - Synthesis and radioactive labeling of biologically active peptides, peptide and protein fragments
PB  - Szegedi Tudományegyetem (SZTE)
PY  - 2009
SP  - 58
UR  - https://m2.mtmt.hu/api/publication/1918264
ID  - 1918264
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Rónai, András
AU  - Király, Kornél P
AU  - Szebeni, Andrea
AU  - Szemenyei, Erzsébet
AU  - Prohászka, Zoltán
AU  - Darula, Zsuzsanna
AU  - Tóth, Géza
AU  - Till, Ibolya
AU  - Szalay, Balázs
AU  - Kató, Erzsébet
AU  - Barna, István
TI  - Immunoreactive endomorphin 2 is generated extracellularly in rat isolated l4,5 dorsal root ganglia by DPP-IV
JF  - REGULATORY PEPTIDES
J2  - REGUL PEPTIDES
VL  - 157
PY  - 2009
IS  - 1-3
SP  - 1
EP  - 2
PG  - 2
SN  - 0167-0115
DO  - 10.1016/j.regpep.2009.06.006
UR  - https://m2.mtmt.hu/api/publication/109882
ID  - 109882
N1  - Megjegyzés-21855716
Megjegyzés-10072901
AB  - BACKGROUND AND AIMS: The gene(s) encoding for endomorphin precursor(s) is/are still unknown. We have raised the possibility of and did find some evidence for a potential de novo biosynthetic route starting from Tyr-Pro precursor. To pursue further this possibility we measured the generation of immunoreactive endomorphin-2 (E2-IR) in adult rat isolated L4,5 dorsal root ganglia. RESULTS AND CONCLUSIONS: In rat isolated dorsal root ganglia the combination of presumed biosynthetic precursor of endomorphin 2 (E2), Tyr-Pro with the dipeptidyl peptidase IV (DPP-IV) inhibitor Ile-Pro-Ile generated 1.60+/-0.37 pg/mg Wet Tissue Weight_30 min E2-IR in the bathing fluid (n=4) with an 8-fold increase upon depolarization whereas the tissue content was low (0.50+/-0.08 pg/mg_WTW). Substance P, as determined by ELISA in the pilot experiments, was found almost exclusively within the tissues. It is concluded that E2-IR was generated extracellularly by a membrane-bound DPP-IV, which was switched to "synthase" mode by the hydrolase inhibitor Ile-Pro-Ile. DPP-IV was depolarization-sensitive in "synthase" functional mode.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Demaegdt, H
AU  - Smitz, L
AU  - De Backer, JP
AU  - Le, MT
AU  - Bauwens, M
AU  - Szemenyei, Erzsébet
AU  - Tóth, Géza
AU  - Michotte, Y
AU  - Vanderheyden, P
AU  - Vauquelin, G
TI  - Translocation of the insulin-regulated aminopeptidase to the cell surface: detection by radioligand binding
JF  - BRITISH JOURNAL OF PHARMACOLOGY
J2  - BR J PHARMACOL
VL  - 154
PY  - 2008
IS  - 4
SP  - 872
EP  - 881
PG  - 10
SN  - 0007-1188
DO  - 10.1038/bjp.2008.117
UR  - https://m2.mtmt.hu/api/publication/1917905
ID  - 1917905
N1  - Megjegyzés-22145412
DI: 10.1038/bjp.2008.117
AB  - Background and purpose: Insulin-regulated aminopeptidase ( IRAP) and the insulin-dependent glucose transporter GLUT4 colocalize in specific intracellular vesicles (that is, GLUT4 vesicles). These vesicles move slowly to the cell surface, but their translocation is markedly enhanced by insulin, resulting in higher glucose uptake. Previous studies of the insulin-mediated translocation of IRAP to the cell surface have been hampered by the laborious detection of IRAP at the cell surface. We aimed to develop a more direct and faster method to detect IRAP. To this end, we used model systems with well-characterized IRAP: CHO-K1 cells expressing endogenous IRAP and recombinant HEK293 cells expressing human IRAP. A more widespread application of the method was demonstrated by the use of 3T3-L1 adipocytes. Experimental approach: After stimulation of the cells with insulin, internalization of IRAP was inhibited by the addition of phenyl arsine oxide (PAO). Then, cell-surface IRAP was detected by the high-affinity binding of radiolabelled angiotensin (Ang) IV (either I-125 or H-3). Key Results: We monitored the time- and concentration dependence of insulin-mediated translocation of IRAP in both cell lines and 3T3-L1 adipocytes. A plateau was reached between 6 and 8 min, and 10(-7) M insulin led to the highest amount of IRAP at the cell surface. Conclusions and implications: Based on the capacity of the IRAP apoenzyme to display high affinity for radiolabelled Ang IV and on the ability of PAO to inhibit IRAP internalization, we developed a more direct and faster method to measure insulin-mediated translocation of IRAP to the cell surface.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Lukaszuk, A
AU  - Demaegdt, H
AU  - Szemenyei, Erzsébet
AU  - Tóth, Géza
AU  - Tymecka, D
AU  - Misicka, A
AU  - Karoyan, P
AU  - Vanderheyden, P
AU  - Vauquelin, G
AU  - Tourwe, D
TI  - Beta-homo-amino acid scan of angiotensin IV
JF  - JOURNAL OF MEDICINAL CHEMISTRY
J2  - J MED CHEM
VL  - 51
PY  - 2008
IS  - 7
SP  - 2291
EP  - 2296
PG  - 6
SN  - 0022-2623
DO  - 10.1021/jm701490g
UR  - https://m2.mtmt.hu/api/publication/1916846
ID  - 1916846
AB  - Angiotensin IV, a metabolite of angiotensin II, inhibits the enzyme insulin regulated aminopeptidase or IRAP and also, although with lower potency, aminopeptidase-N (AP-N). When both beta(2)-homo amino acid- and beta(3)-homo amino acid substitutions were used, allowed the identification of H-(R) beta(2)hVal-Tyr-Ile-His-Pro-beta(3) hPhe-OH as a potent and stable Ang IV analog with high selectivity for IRAP versus AP-N and the AT1 receptor.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Szemenyei, Erzsébet
AU  - Barna, István
AU  - Mergl, Zsuzsanna
AU  - Keresztes, Attila
AU  - Darula, Zsuzsanna
AU  - Kató, Erzsébet
AU  - Tóth, Géza
AU  - Rónai, András
TI  - Detection of a novel immunoreactive endomorphin 2-like peptide in rat brain extracts
JF  - REGULATORY PEPTIDES
J2  - REGUL PEPTIDES
VL  - 148
PY  - 2008
IS  - 1-3
SP  - 54
EP  - 61
PG  - 8
SN  - 0167-0115
DO  - 10.1016/j.regpep.2008.03.001
UR  - https://m2.mtmt.hu/api/publication/110000
ID  - 110000
N1  - Megjegyzés-22169812
Megjegyzés-22152745
DI: 10.1016/j.regpep.2008.03.001
AB  - To pursue further the possible de novo biosynthetic pathway of endomorphins in rat brain we raised antibodies to endomorphin-2 conjugate in rabbits. Antiserum R1 recognized endomorphin-2 with good selectivity as compared to endomorphin-1 with a median detection value of 65.5+/-7.5 pg/tube (n=7), whereas R4 antiserum recognized both endomorphins with similar sensitivity. Neither antisera recognized YP-related di- or tripeptides or YGGF-related opioid sequences (enkephalins, beta-endorphin, dynorphin). Using the same rat brain extraction-RP-HPLC-gradient separation paradigm as previously, antisera detected 144.6+/-40.0 (n=3) pg/g wet brain weight endomorphin-2-like immunoreactivity in the fraction corresponding to standard endomorphin-2 retention time and also in the fraction matching endomorphin-2-OH standard retention time (179.1+/-30.1 pg/g). Since R1 failed to recognize authentic endomorphin-2-OH, the second immunoreactive species must be different from both endomorphin-2 and endomorphin-2-OH. Possible biosynthetic intermediates to endomorphins, synthetic YPFFG and YPWFG had retention times close to the parent endomorphin standards in RP-HPLC gradient separation profile. The former was a mu-opioid receptor agonist of medium potency in the in vitro assays (rat brain RBA>PgammaS binding and mouse vas deferens), whereas the latter was a weak mu-opioid receptor agonist with a significant delta-opioid receptorial action as well and a definite indication of partial agonism.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Szemenyei, Erzsébet
AU  - Tóth, Géza
TI  - Tritium labelling and degradation studies of Dmt1-endomorphin 2
JF  - JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
J2  - J LABELLED COMPD RAD
VL  - 50
PY  - 2007
SP  - 1148
EP  - 1152
PG  - 5
SN  - 0362-4803
DO  - 10.1002/jlcr.1402
UR  - https://m2.mtmt.hu/api/publication/1915370
ID  - 1915370
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Rónai, András
AU  - Szemenyei, Erzsébet
AU  - Kató, Erzsébet
AU  - Kocsis, László
AU  - Orosz, György
AU  - Al-Khrasani, Mahmoud
AU  - Tóth, Géza
TI  - Endomorphin synthesis in rat brain from intracerebroventricularly injected [H-3]-Tyr-Pro: A possible biosynthetic route for endomorphins
JF  - REGULATORY PEPTIDES
J2  - REGUL PEPTIDES
VL  - 134
PY  - 2006
IS  - 1
SP  - 54
EP  - 60
PG  - 7
SN  - 0167-0115
DO  - 10.1016/j.regpep.2005.12.004
UR  - https://m2.mtmt.hu/api/publication/1626916
ID  - 1626916
N1  - Cited By :17            
            Export Date: 29 May 2022            
            CODEN: REPPD
AB  - in spite of concentrated efforts, the biosynthetic route of mu-opioid receptor agonist brain tetrapeptide endomorphins (Tyr-Pro-Trp-Phe-NH2 and Tyr-Pro-Phe-Phe-NH2), discovered in 1997, is still obscure. We report presently that 30 min after intracerebroventricular injection of 20 or 200 mu Ci [H-3]Tyr-Pro (49.9 Ci mmol(-1)) the incorporated radioactivity was found in endomorphin-related tetra- and tripeptides in rat brain extracts. As detected by the combination of HPLC with radiodetection, a peak corresponding to endomorphin-2-OH could be identified in two of four extracts of "20 mu Ci" series. Radioactive peaks in position of Tyr, Tyr-Pro, Tyr-Pro-Phe or Tyr-Pro-Trp appeared regularly in both series and also in the "tetrapeptide cluster" constituted by endomorphins and their free carboxylic forms. In one of the four extracts in the "200 mu Ci" series a robust active peak in the position of endomorphin 2 could be detected. Intracerebroventricularly injected 100 mmol, but not 10 or 1000 nmol cold Tyr-Pro (devoid of opioid activity in vitro), caused a naloxone-reversible prolongation of tail-flick latency in rats, peaking between 15 and 30 min. We suggest that Tyr-Pro may serve as a biosynthetic precursor to endomorphin synthesis. (C) 2006 Elsevier B.V. All rights reserved.
LA  - English
DB  - MTMT
ER  -