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Titolo:
CLONING AND FUNCTIONAL-CHARACTERIZATION THROUGH ANTISENSE MAPPING OF A KAPPA(3)-RELATED OPIOID RECEPTOR
Autore:
PAN YX; CHENG J; XU J; ROSSI G; JACOBSON E; RYANMORO J; BROOKS AI; DEAN GE; STANDIFER KM; PASTERNAK GW;
Indirizzi:
MEM SLOAN KETTERING CANC CTR,DEPT NEUROL,COTZIAS LAB NEUROONCOL,1275 YORK AVE NEW YORK NY 10021 MEM SLOAN KETTERING CANC CTR,DEPT NEUROL,COTZIAS LAB NEUROONCOL NEW YORK NY 10021 CORNELL UNIV,COLL MED,DEPT NEUROL NEW YORK NY 10021 CORNELL UNIV,COLL MED,DEPT NEUROSCI & PHARMACOL NEW YORK NY 10021 UNIV CINCINNATI,COLL MED,DEPT MOLEC GENET BIOCHEM & MICROBIOL CINCINNATI OH 45267
Titolo Testata:
Molecular pharmacology
fascicolo: 6, volume: 47, anno: 1995,
pagine: 1180 - 1188
SICI:
0026-895X(1995)47:6<1180:CAFTAM>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHARMACOLOGICAL CHARACTERIZATION; OPIATE RECEPTOR; NALOXONE BENZOYLHYDRAZONE; MU-OPIATE; EXPRESSION; KAPPA; BRAIN; CDNA; BINDING; SUBTYPES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
Y.X. Pan et al., "CLONING AND FUNCTIONAL-CHARACTERIZATION THROUGH ANTISENSE MAPPING OF A KAPPA(3)-RELATED OPIOID RECEPTOR", Molecular pharmacology, 47(6), 1995, pp. 1180-1188

Abstract

We have identified a putative opioid receptor from mouse brain (KOR-3), belonging to the G protein-coupled receptor family, that is distinct from the previously cloned mu, delta, and kappa(1) receptors. Assignment of the clone to the opioid receptor family derives from both structural and functional studies. Its predicted amino acid sequence is highly homologous to that of the other opioid receptors, particularly inmany of the transmembrane regions, where long stretches are identicalto mu, delta, and kappa(1) receptors. Both cyclazocine and nalorphineinhibit cAMP accumulation in COS-7 cells stably expressing the clone. Northern analysis shows that the mRNA is present in brain but not in a number of other organs. Southern analysis suggests a single gene encoding the receptor. A highly selective monoclonal antibody directed against the native kappa(3) receptor recognizes, in Western analysis, the clone expressed in COS-7 cells. The in vitro translation product is also labeled by the antibody. Additional clones reveal the presence ofseveral introns, including one in the second extracellular loop and another in the first transmembrane region. Antisense studies with an oligodeoxynucleotide directed against a region of the second extracellular loop reveal a selective blockade of kappa(3) analgesia in vivo thatis not observed with a mismatch oligodeoxynucleotide based upon the antisense sequence. The mu, delta, and kappa(1) analgesia is unaffectedby this antisense treatment. Antisense mapping of the clone downstream from the splice site in the first transmembrane region reveals that six different antisense oligodeoxynucleotides all block kappa(3) analgesia. In contrast, only one of an additional six different antisense oligodeoxynucleotides directed at regions upstream from this splice site is effective. This strong demarcation between the two regions raisesthe possibility of splice variants of the receptor. An additional clone reveals an insert in the 3' untranslated region. In conclusion, theantibody and antisense studies strongly associate KOR-3 with the kappa(3)-opioid receptor, although it is not clear whether it is the kappa(3) receptor itself or a splice variant.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 23:56:56