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Titolo:
In vitro studies of striatal vesicles containing the vesicular monoamine transporter (VMAT2): Rat versus mouse differences in sequestration of 1-methyl-4-phenylpyridinium
Autore:
Staal, RGW; Hogan, KA; Liang, CL; German, DC; Sonsalla, PK;
Indirizzi:
Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, Piscataway, NJ 08854 USA Univ Med & Dent New Jersey Piscataway NJ USA 08854 scataway, NJ 08854 USA Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA Univ Texas Dallas TX USA exas, SW Med Ctr, Dept Psychiat, Dallas, TX USA
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 2, volume: 293, anno: 2000,
pagine: 329 - 335
SICI:
0022-3565(200005)293:2<329:IVSOSV>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
DOPAMINERGIC NEUROTOXIN 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; SYNAPTIC VESICLES; CHROMAFFIN GRANULES; SPECIES SENSITIVITY; CELLULAR-RESISTANCE; MPTP NEUROTOXICITY; KNOCKOUT MICE; TOXICITY; BINDING; INHIBITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Sonsalla, PK Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, DeptNeurol, 675 Hoes Lane, Piscataway, NJ 08854 USA Univ Med & Dent New Jersey675 Hoes Lane Piscataway NJ USA 08854
Citazione:
R.G.W. Staal et al., "In vitro studies of striatal vesicles containing the vesicular monoamine transporter (VMAT2): Rat versus mouse differences in sequestration of 1-methyl-4-phenylpyridinium", J PHARM EXP, 293(2), 2000, pp. 329-335

Abstract

Significant differences exist in the sensitivity of mice and rats to the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that cannot be explained by differences in exposure to or uptake of 1-methyl-4-phenylpyridinium (MPP+) into dopamine (DA) neurons. MPP+ is also a substrate for the brain vesicular monoamine transporter (VMAT2), and sequestration into synaptic vesicles may be one mechanism of protection against MPP+ toxicity. A greater sequestration of MPP+ into vesicles of DA neurons in rats versus mice could explain the lower vulnerability of DA neurons in the rat to MPP+ toxicity. To test this hypothesis, the kinetics of uptake for [H-3]MPPand [H-3]DA as well as [H-3]dihydrotetrabenazine binding to VMAT2 were compared in vesicles isolated from the striata of rats and mice. The K-m valueof [H-3]MPP+ transport was similar in the two species. In contrast, the maximal transport rate (V-max) was 2-fold greater in vesicles from rats than in those from mice. Likewise, the K-m value for [H-3]DA transport was similar in both preparations, but the V-max value was 2-fold greater in rat thanin mouse vesicles. The B-max value for [H-3]dihydrotetrabenazine binding was also 2-fold greater in striatal vesicles from rats than in those from mice. Electron micrographs demonstrated that vesicles isolated from rats and mice were approximately the same size. Based on these observations, we propose that striatal vesicles from rats have more VMAT2 than vesicles from mice and that this species difference in VMAT2 density may help explain the reduced vulnerability of rat DA neurons to MPP+ neurotoxicity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/07/20 alle ore 05:34:49