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Titolo:
Reduced antinociception in mice lacking neuronal nicotinic receptor subunits
Autore:
Marubio, LM; Arroyo-Jimenez, MD; Cordero-Erausquin, M; Lena, C; Le Novere, N; dExaerde, AD; Huchet, M; Damaj, MI; Changeux, JP;
Indirizzi:
Inst Pasteur, CNRS, UA D1284, F-75724 Paris 15, France Inst Pasteur Paris France 15 r, CNRS, UA D1284, F-75724 Paris 15, France Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol, Richmond, VA Virginia Commonwealth Univ Richmond VA USA 23298 Pharmacol, Richmond, VA
Titolo Testata:
NATURE
fascicolo: 6730, volume: 398, anno: 1999,
pagine: 805 - 810
SICI:
0028-0836(19990429)398:6730<805:RAIMLN>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
NUCLEUS RAPHE MAGNUS; CENTRAL NERVOUS-SYSTEM; ACETYLCHOLINE-RECEPTORS; ANALGESIC ACTIVITY; RAT-BRAIN; MODULATION; THALAMUS; GENE; PAIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Life Sciences
Physical, Chemical & Earth Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Changeux, JP Inst Pasteur, CNRS, UA D1284, 28 Rue Dr Roux, F-75724 Paris 15, France Inst Pasteur 28 Rue Dr Roux Paris France 15 Paris 15, France
Citazione:
L.M. Marubio et al., "Reduced antinociception in mice lacking neuronal nicotinic receptor subunits", NATURE, 398(6730), 1999, pp. 805-810

Abstract

Nicotine exerts antinociceptive effects by interacting with one or more ofthe subtypes of nicotinic acetylcholine receptors (nAChRs) that are present throughout the neuronal pathways that respond to pain(1-5). To identify the particular subunits involved in this process, we generated mice lacking the alpha 4 subunit of the neuronal nAChR by homologous recombination techniques and studied these together with previously generated mutant mice lacking the beta 2 nAChR subunit(6). Here we show that the homozygous alpha 4(-/-) mice no longer express high-affinity [H-3]nicotine and [H-3]epibatidinebinding sites throughout the brain. In addition, both types of mutant micedisplay a reduced antinociceptive effect of nicotine on the hot-plate testand diminished sensitivity to nicotine in the tail-flick test. Patch-clamprecordings further reveal that raphe magnus and thalamic neurons no longerrespond to nicotine. The alpha 4 nAChR subunit, possibly associated with the beta 2 nAChR subunit, is therefore crucial for nicotine-elicited antinociception.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/09/20 alle ore 17:16:18