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Titolo:
Generation and pharmacological analysis of M-2 and M-4 muscarinic receptorknockout mice
Autore:
Gomeza, J; Zhang, L; Kostenis, E; Felder, CC; Bymaster, FP; Brodkin, J; Shannon, H; Xia, B; Duttaroy, A; Deng, CX; Wess, J;
Indirizzi:
NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA NIDDKD Bethesda MD USA 20892 D, Bioorgan Chem Lab, Bethesda, MD 20892 USA NIDDKD, Biochem & Metab Lab, Bethesda, MD 20892 USA NIDDKD Bethesda MD USA 20892 Biochem & Metab Lab, Bethesda, MD 20892 USA Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA Eli Lilly & CoIndianapolis IN USA 46285 Labs, Indianapolis, IN 46285 USA
Titolo Testata:
LIFE SCIENCES
fascicolo: 22-23, volume: 68, anno: 2001,
pagine: 2457 - 2466
SICI:
0024-3205(20010427)68:22-23<2457:GAPAOM>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT SPINAL-CORD; ACETYLCHOLINE-RECEPTORS; ANTINOCICEPTION; DOPAMINE; PROTEINS; SUBTYPES; NEURONS; D1; M2; M1;
Keywords:
gene targeting; oxotremorine; analgesia; locomotor activity; striatum; Parkinson's disease; dopamine receptor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
22
Recensione:
Indirizzi per estratti:
Indirizzo: Wess, J NIDDKD, Bioorgan Chem Lab, Bldg 8A,Room B1A-05,8 Ctr Dr MSC 0810, Bethesda, MD 20892 USA NIDDKD Bldg 8A,Room B1A-05,8 Ctr Dr MSC 0810 Bethesda MD USA 20892
Citazione:
J. Gomeza et al., "Generation and pharmacological analysis of M-2 and M-4 muscarinic receptorknockout mice", LIFE SCI, 68(22-23), 2001, pp. 2457-2466

Abstract

Muscarinic acetylcholine receptors (M-1-M-5) play important roles in the modulation of many key functions of the central and peripheral nervous system. To explore the physiological roles of the two G(i)-coupled muscarinic receptors, we disrupted the M-2 and M-4 receptor genes in mice by using a gene targeting strategy, pharmacological and behavioral analysis of the resulting mutant mice showed that the M-2 receptor subtype is critically involvedin mediating three of the most striking central muscarinic effects, tremor, hypothermia, and analgesia. These studies also indicated that M-4 receptors are not critically involved in these central muscarinic responses. However, M-4 receptor-deficient mice showed an increase in basal locomotor activity and greatly enhanced locomotor responses following drug-induced activation of D1 dopamine receptors, This observation is consistent with the concept that M-4 receptors exert inhibitory control over D1 receptor-mediated locomotor stimulation, probably at the level of striatal projection neurons where the two receptors are known to be coexpressed. These findings emphasize the usefulness of gene targeting approaches to shed light on the physiological and pathophysiological roles of the individual muscarinic receptor subtypes. (C) 2001 Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 10:22:41