Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Characterization of (S)-des-4-amino-3-[I-125]iodozacopride ([I-125]DAIZAC), a selective high-affinity radioligand for 5-hydroxytryptamine(3) receptors
Autore:
Hewlett, WA; Trivedi, BL; Zhang, ZJ; de Paulis, T; Schmidt, DE; Lovinger, DM; Ansari, MS; Ebert, MH;
Indirizzi:
Vanderbilt Univ, Med Ctr, Dept Psychiat, Sch Med, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 , Sch Med, Nashville, TN 37232 USA Vanderbilt Univ, Sch Med, Dept Radiol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 pt Radiol, Nashville, TN 37232 USA VanderbiltSAniv, Sch Med, Dept Physiol & Mol Biophys, Nashville, TN 37232 U Vanderbilt Univ Nashville TN USA 37232 Mol Biophys, Nashville, TN 37232 U
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 1, volume: 288, anno: 1999,
pagine: 221 - 231
SICI:
0022-3565(199901)288:1<221:CO((>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHARMACOLOGICAL CHARACTERIZATION; SEROTONIN 5-HT3; GUINEA-PIG; RECOGNITION SITES; H-3 RS-42358-197; 5HT(3) RECEPTORS; BINDING-SITES; RAT-BRAIN; ANTAGONISTS; LIGAND;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Hewlett, WA Vanderbilt32niv, Med Ctr, Dept Psychiat, Sch Med, A-2207, Nashville, TN 372 Vanderbilt Univ A-2207 Nashville TN USA 37232 ashville, TN 372
Citazione:
W.A. Hewlett et al., "Characterization of (S)-des-4-amino-3-[I-125]iodozacopride ([I-125]DAIZAC), a selective high-affinity radioligand for 5-hydroxytryptamine(3) receptors", J PHARM EXP, 288(1), 1999, pp. 221-231

Abstract

The 5-hydroxytryptamine(HT)(3) receptor subtype is present in the central nervous system (CNS) in low abundance, and few selective radiolabeled antagonists with high specific activity are available to study these sites. DAIZAC [desamino-3-iodo-(S)zacopride; (S)-5-chloro-3-iodo-2-methoxy-N-(1-azobicyclo-[2.2.2]oct-3-yl)benzamide] is a compound with high affinity and selectivity for the 5-HT3 receptor. Scatchard analysis of specific binding to NCB-20 cell membranes gave a B-max of 340 +/- 58 fmol/mg protein and a K-D of 0.14 +/- 0.03 nM, which is in agreement with the value previously reported in rat brain (K-D = 0.15 nM). Nonspecific binding of [I-125]DAIZAC in NCB-20 cells was <1% of total binding at the K-D for DAIZAC compared with 17% inthe rat brain preparation. Unlabeled DAIZAC (10 mu M) showed minimal ability to displace binding of radiolabeled ligands selected for their affinities for other CNS receptor and uptake carrier binding sites. The discrimination ratio of DAIZAC for the 5-HT3 receptor over the M-1 muscarinic binding site, the non-5-HT3 site at which it was most potent, was >2800. Serotonergic antagonists at every other known CNS serotonergic binding sites (3-30 mu M) were ineffective in displacing [I-125]DAIZAC binding in rat brain membranes. Similarly, antagonists (3-30 mu M) for other nonserotonergic receptorsand uptake sites were ineffective in displacing [I-125]DAIZAC binding. Autoradiographic studies showed highest specific binding in area postrema and nucleus solitarius, with intermediate levels of binding in entorhinal cortex and hippocampus. DAIZAC inhibited 5-HT3 receptor-mediated inward cation current in NCB-20 cells with an IC50 of 0.24 nM. [I-125]DAIZAC is a potent and highly selective ligand for in vitro studies of the 5-HT3 receptor.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 01:37:10