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Titolo:
Differential knockdown of delta-opioid receptor subtypes in the rat brain by antisense oligodeoxynucleotides targeting mRNA
Autore:
Negri, L; Lattanzi, R; Borsodi, A; Toth, G; Salvadori, S;
Indirizzi:
Univ La Sapienza, Inst Med Pharmacol, I-00185 Rome, Italy Univ La Sapienza Rome Italy I-00185 t Med Pharmacol, I-00185 Rome, Italy Hungarian Acad Sci, Biol Res Ctr, H-6701 Szeged, Hungary Hungarian Acad Sci Szeged Hungary H-6701 Res Ctr, H-6701 Szeged, Hungary Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy Univ Ferrara Ferrara Italy I-44100 harmaceut Sci, I-44100 Ferrara, Italy Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy Univ Ferrara Ferrara Italy I-44100 tr Biotechnol, I-44100 Ferrara, Italy
Titolo Testata:
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT
fascicolo: 2, volume: 9, anno: 1999,
pagine: 203 - 211
SICI:
1087-2906(199904)9:2<203:DKODRS>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
SELECTIVELY BLOCKS; MU-AGONIST; IN-VIVO; ANTINOCICEPTION; MICE; NALTRINDOLE; MORPHINE; BINDING; MOUSE; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Negri, L Univ La Sapienza, Inst Med Pharmacol, Piazza A Moro 5, I-00185 Rome, Italy Univ La Sapienza Piazza A Moro 5 Rome Italy I-00185 Rome, Italy
Citazione:
L. Negri et al., "Differential knockdown of delta-opioid receptor subtypes in the rat brain by antisense oligodeoxynucleotides targeting mRNA", ANTISENSE N, 9(2), 1999, pp. 203-211

Abstract

Two antisense oligodeoxynucleotides (A-ODN), targeting delta-opioid receptor mRNA (DOR) and two mismatch ODN sequences (mODN) were continuously infused for 24 days into the lateral brain ventricles of Wistar rats. The density of delta-opioid receptors in rat brain homogenates was measured by saturation binding experiments using four selective ligands, two agonists ([D-Ala(2), Glu(4)]-deltorphin and DPDPE) and two antagonists (Dmt-Tic-OH and naltrindole), and by immunoblotting SDS solubilized receptor protein, In brain membranes of mODN or saline-infused rats, the rank order of delta-opioid receptor density, calculated by B-max values of the four delta-opioid receptor ligands, was: [D-Ala(2), Glu(4)]deltorphin congruent to Dmt-Tic-OH congruent to naltrindole (86-118 fmol/mg protein) > DPDPE (73.6 +/- 6.3 fmol/mg protein). At the end of the 24 day infusion of A-ODN targeting DOR nucleotide sequence 280-299 (A-ODN280-299), the B-max of DPDPE (62.4 +/- 3.2 fmol/mgprotein) was significantly higher than that of Dmt-Tic-OH (31.5 +/- 3.9 fmol/mg protein), Moreover, both the K-d value for DPDPE saturation binding and the Y value for Dmt-Tic-OH displacement by DPDPE were halved. In contrast, an A-ODN treatment targeting exon 3 (A-ODN741-760) decreased the specific binding of [D-Ala(2), Glu(4)]deltorphin and Dmt-Tic-OH significantly less(67%-81%) than the binding of DPDPE (53%), without changes in DPDPE K-i and K-D values. No A-ODN treatment modified the specific binding of the delta-opioid agonist DAMGO and of the k-selective opioid receptor ligand U69593,On the Western blot of solubilized striatum proteins, A-ODN280-299 and A-ODN741-760 downregulated the levels of the DOR protein, whereas the corresponding mODN were inactive. The 24-day infusion of A-ODN280-299 inhibited therat locomotor response to [D-Ala(2), Glu(4)]deltorphin but not to DPDPE, Intracerebroventricular (i.c.v.) infusion of A-ODN741-760 reduced the locomotor responses to both delta-opioid receptor agonists, whereas mODN infusionnever affected agonist potencies. In conclusion, these results demonstratethat 24-day continuous i.c.v. infusion of A-ODN targeting the nucleotide sequence 280-299 of DOR can differentially knockdown delta(1) and delta(2) binding sites in the rat brain.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/05/20 alle ore 15:16:42