Pyroglutamyl peptidase II inhibition specifically increases recovery of TRH released from rat brain slices

J. L. Charli; M. Mendez; M. A. Vargas; M. Cisneros; M. Assai; P. Joseph-Bravo; S. Wilk

doi:10.1016/0143-4179(89)90044-9

Pyroglutamyl peptidase II inhibition specifically increases recovery of TRH released from rat brain slices

J. L. Charli
, M. Mendez
, M. A. Vargas
, M. Cisneros
, M. Assai
, P. Joseph-Bravo
, S. Wilk

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

Pyroglutamyl peptidase II (EC 3.4.19-) is a highly specific membrane-bound thyrotropin releasing hormone (TRH) degrading enzyme. To study the functional significance of pyroglutamyl peptidase II in TRH degradation, we synthesized the reversible inhibitor N-1-carboxy-2-phenylethyl (N^imbenzyl)-histidyl-β-naphthylamide (CPHNA). CPHNA inhibited the enzyme with a Ki of 8 μM, but had no effect no TRH receptors or no prolyl endopeptidase (EC 3.4.21.26). It weakly inhibited cytosolic pyroglutamyl peptidase I (EC 3.4.19.3). CPHNA at a concentration of 10^-4 M increased both the basal and potassium stimulated recovery of TRH released from hypothalamic slices by approximately two-fold. An even higher recovery was observed in slices from brain regions with relatively high levels of pyroglutamyl peptidase II. CPHNA had no effect on the basal recovery of γ-aminobutyric acid or Met-enkephalin released from brain slices but decreased the potassium stimulated recovery of both Met-enkephalin and γ-aminobutyric acid. These data further support the involvement of pyroglutamyl peptidase II in the extracellular inactivation of brain TRH.

Original language	English
Pages (from-to)	191-196
Number of pages	6
Journal	Neuropeptides
Volume	14
Issue number	3
DOIs	https://doi.org/10.1016/0143-4179(89)90044-9
State	Published - Oct 1989
Externally published	Yes

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title = "Pyroglutamyl peptidase II inhibition specifically increases recovery of TRH released from rat brain slices",

abstract = "Pyroglutamyl peptidase II (EC 3.4.19-) is a highly specific membrane-bound thyrotropin releasing hormone (TRH) degrading enzyme. To study the functional significance of pyroglutamyl peptidase II in TRH degradation, we synthesized the reversible inhibitor N-1-carboxy-2-phenylethyl (Nimbenzyl)-histidyl-β-naphthylamide (CPHNA). CPHNA inhibited the enzyme with a Ki of 8 μM, but had no effect no TRH receptors or no prolyl endopeptidase (EC 3.4.21.26). It weakly inhibited cytosolic pyroglutamyl peptidase I (EC 3.4.19.3). CPHNA at a concentration of 10-4 M increased both the basal and potassium stimulated recovery of TRH released from hypothalamic slices by approximately two-fold. An even higher recovery was observed in slices from brain regions with relatively high levels of pyroglutamyl peptidase II. CPHNA had no effect on the basal recovery of γ-aminobutyric acid or Met-enkephalin released from brain slices but decreased the potassium stimulated recovery of both Met-enkephalin and γ-aminobutyric acid. These data further support the involvement of pyroglutamyl peptidase II in the extracellular inactivation of brain TRH.",

author = "Charli, \{J. L.\} and M. Mendez and Vargas, \{M. A.\} and M. Cisneros and M. Assai and P. Joseph-Bravo and S. Wilk",

year = "1989",

month = oct,

doi = "10.1016/0143-4179(89)90044-9",

language = "English",

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journal = "Neuropeptides",

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T1 - Pyroglutamyl peptidase II inhibition specifically increases recovery of TRH released from rat brain slices

AU - Charli, J. L.

AU - Mendez, M.

AU - Vargas, M. A.

AU - Cisneros, M.

AU - Assai, M.

AU - Joseph-Bravo, P.

AU - Wilk, S.

PY - 1989/10

Y1 - 1989/10

N2 - Pyroglutamyl peptidase II (EC 3.4.19-) is a highly specific membrane-bound thyrotropin releasing hormone (TRH) degrading enzyme. To study the functional significance of pyroglutamyl peptidase II in TRH degradation, we synthesized the reversible inhibitor N-1-carboxy-2-phenylethyl (Nimbenzyl)-histidyl-β-naphthylamide (CPHNA). CPHNA inhibited the enzyme with a Ki of 8 μM, but had no effect no TRH receptors or no prolyl endopeptidase (EC 3.4.21.26). It weakly inhibited cytosolic pyroglutamyl peptidase I (EC 3.4.19.3). CPHNA at a concentration of 10-4 M increased both the basal and potassium stimulated recovery of TRH released from hypothalamic slices by approximately two-fold. An even higher recovery was observed in slices from brain regions with relatively high levels of pyroglutamyl peptidase II. CPHNA had no effect on the basal recovery of γ-aminobutyric acid or Met-enkephalin released from brain slices but decreased the potassium stimulated recovery of both Met-enkephalin and γ-aminobutyric acid. These data further support the involvement of pyroglutamyl peptidase II in the extracellular inactivation of brain TRH.

AB - Pyroglutamyl peptidase II (EC 3.4.19-) is a highly specific membrane-bound thyrotropin releasing hormone (TRH) degrading enzyme. To study the functional significance of pyroglutamyl peptidase II in TRH degradation, we synthesized the reversible inhibitor N-1-carboxy-2-phenylethyl (Nimbenzyl)-histidyl-β-naphthylamide (CPHNA). CPHNA inhibited the enzyme with a Ki of 8 μM, but had no effect no TRH receptors or no prolyl endopeptidase (EC 3.4.21.26). It weakly inhibited cytosolic pyroglutamyl peptidase I (EC 3.4.19.3). CPHNA at a concentration of 10-4 M increased both the basal and potassium stimulated recovery of TRH released from hypothalamic slices by approximately two-fold. An even higher recovery was observed in slices from brain regions with relatively high levels of pyroglutamyl peptidase II. CPHNA had no effect on the basal recovery of γ-aminobutyric acid or Met-enkephalin released from brain slices but decreased the potassium stimulated recovery of both Met-enkephalin and γ-aminobutyric acid. These data further support the involvement of pyroglutamyl peptidase II in the extracellular inactivation of brain TRH.

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U2 - 10.1016/0143-4179(89)90044-9

DO - 10.1016/0143-4179(89)90044-9

M3 - Article

C2 - 2575716

AN - SCOPUS:0024384817

SN - 0143-4179

VL - 14

SP - 191

EP - 196

JO - Neuropeptides

JF - Neuropeptides

IS - 3

ER -

Pyroglutamyl peptidase II inhibition specifically increases recovery of TRH released from rat brain slices

Abstract

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