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-beta-naphthylamide (CPHNA). CPHNA inhibited the enzyme with a Ki of 8 microM, 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 gamma-aminobutyric acid or Met-enkephalin released from brain slices but decreased the potassium stimulated recovery of both Metenkephalin and gamma-aminobutyric acid. These data further support the involvement of pyroglutamyl peptidase II in the extracellular inactivation of brain TRH.
authors.affiliation: Departamento de Bioquimica, Universidad Nacional Autonoma de Mexico, Cuernavaca Mor.
authors.forename: J L
authors.initials: JL
authors.lastname: Charli
authors.forename: M
authors.initials: M
authors.lastname: Mendez
authors.forename: M A
authors.initials: MA
authors.lastname: Vargas
authors.forename: M
authors.initials: M
authors.lastname: Cisneros
authors.forename: M
authors.initials: M
authors.lastname: Assai
authors.forename: P
authors.initials: P
authors.lastname: Joseph-Bravo
authors.forename: S
authors.initials: S
authors.lastname: Wilk
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D001921:Brain / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D011751:Pyroglutamyl-Peptidase I / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C062382:N-1-carboxy-2-phenylethyl(N(im)benzyl)histidyl-beta-naphthylamide; D009281:Naphthalenes; D013973:Thyrotropin-Releasing Hormone; D000626:Aminopeptidases; D011751:Pyroglutamyl-Peptidase I