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Titolo:
Effect of graded hypoxia on the high-affinity CPP binding site of the NMDAreceptor in the cerebral cortex of newborn piglets
Autore:
Fritz, KI; Zanelli, S; Mishra, OP; Delivoria-Papadopoulos, M;
Indirizzi:
Med Coll Penn & Hahnemann Univ, St Christophers Hosp Children, Dept Pediat, Philadelphia, PA 19129 USA Med Coll Penn & Hahnemann Univ Philadelphia PA USA 19129 ia, PA 19129 USA
Titolo Testata:
BRAIN RESEARCH
fascicolo: 1-2, volume: 891, anno: 2001,
pagine: 266 - 273
SICI:
0006-8993(20010209)891:1-2<266:EOGHOT>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
D-ASPARTATE RECEPTOR; GUINEA-PIG BRAIN; 3-((+/-)-2-CARBOXYPIPERAZIN-4-YL)PROPYL-1-PHOSPHONIC ACID CPP; LIPID-PEROXIDATION; RAT-BRAIN; ANTAGONISTS; MECHANISMS; INVITRO; PREVENTION; MEMBRANES;
Keywords:
newborn; brain; NMDA receptor; CPP; hypoxia; lipid peroxidation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Fritz, KI Med Coll Penn & Hahnemann Univ, St Christophers Hosp Children, Dept Pediat, 3300 Henry Ave,7th Floor Heritage Bldg, Philadelphia, PA 19129 USA Med Coll Penn & Hahnemann Univ 3300 Henry Ave,7th Floor Heritage Bldg Philadelphia PA USA 19129
Citazione:
K.I. Fritz et al., "Effect of graded hypoxia on the high-affinity CPP binding site of the NMDAreceptor in the cerebral cortex of newborn piglets", BRAIN RES, 891(1-2), 2001, pp. 266-273

Abstract

Previous studies have shown that the N-methyl-D-aspartate (NMDA) receptor is modified during hypoxia in the cerebral cortex of newborn piglets. The present study tests the hypothesis that the NMDA receptor 3-(2-carbaxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) high-affinity binding site is modified during hypoxia and that the degree of modification correlates with the progressive decrease in cerebral cellular energy metabolism and increase inlipid peroxidation induced by hypoxia. Studies were conducted in twelve anesthetized, ventilated newborn piglets, five normoxic and seven hypoxic which were exposed to decreased fraction of inspired oxygen (FiO(2)) to achieve varying phosphocreatine (PCr) levels. (3)[H]-CPP binding was performed with CPP concentrations ranging from 0.5 to 1500 nM at 23 degreesC for 40 minin P-2 membrane fractions. Brain tissue PCr levels were determined biochemically. Conjugated dienes (CDs) were measured as an index of lipid peroxidation. Ln the normoxic group, B-max (receptor number) fur the CPP binding sire was 329+/-93 fmol/mg protein and K-d (dissociation constant) 137+/-44 nM, the mean PCr value was 2.5+/-0.4 mu mol/g brain and the CD level was 0.0 nmol/g brain. As tissue hypoxia worsened, there was a gradual decline in tissue PCr as well as receptor B-max and K-d values, and there was an increase in conjugated dienes. Both the receptor B-max (r=0.90) and K-d (r=0.72) decreased in a linear relationship as PCr decreased. As the levels of CDs increased both the receptor B-max (r=0.88) and K-d (r=0.68) decreased in a linear fashion. The data show that there is not a critical hypoxic threshold for modification of the CPP binding site of the NMDA receptor, but that modification is coupled to a gradual decrease in brain cell energy metabolism and increase in lipid peroxidation. We speculate that hypoxia-induced modification of the NMDA receptor is mediated not only by changes in the receptor recognition site but also by an alteration of brain cell membrane structure secondary to conjugated diene formation. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/04/20 alle ore 02:33:23