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Titolo:
ELECTROPHYSIOLOGICAL CHARACTERIZATION OF TACHYKININ RECEPTORS IN THE RAT NUCLEUS OF THE SOLITARY TRACT AND DORSAL MOTOR NUCLEUS OF THE VAGUS IN-VITRO
Autore:
MAUBACH KA; JONES RSG;
Indirizzi:
UNIV BRISTOL,SCH MED SCI,DEPT PHYSIOL,UNIV WALK BRISTOL BS8 1TD AVON ENGLAND UNIV OXFORD,DEPT PHARMACOL OXFORD OX1 3QT ENGLAND
Titolo Testata:
British Journal of Pharmacology
fascicolo: 6, volume: 122, anno: 1997,
pagine: 1151 - 1159
SICI:
0007-1188(1997)122:6<1151:ECOTRI>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
CENTRAL-NERVOUS-SYSTEM; GUINEA-PIG ILEUM; SUBSTANCE-P; NK1 RECEPTOR; INDUCED EMESIS; AREA POSTREMA; SELECTIVE AGONISTS; NEONATAL RAT; NEUROKININ-1 RECEPTOR; NONPEPTIDE ANTAGONIST;
Keywords:
SUBSTANCE P; NEUROKININ A; NUCLEUS OF THE SOLITARY TRACT; DORSAL MOTOR NUCLEUS OF THE VAGUS; EMESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
64
Recensione:
Indirizzi per estratti:
Citazione:
K.A. Maubach e R.S.G. Jones, "ELECTROPHYSIOLOGICAL CHARACTERIZATION OF TACHYKININ RECEPTORS IN THE RAT NUCLEUS OF THE SOLITARY TRACT AND DORSAL MOTOR NUCLEUS OF THE VAGUS IN-VITRO", British Journal of Pharmacology, 122(6), 1997, pp. 1151-1159

Abstract

1 Recent studies have shown antagonists at the NK1 subtype of receptor for tachykinins are antiemetics and suggested that this may result from blockade of tachykinin-mediated synaptic transmission at a centralsite in the emetic reflex. 2 We have used intracellular recording in vitro to study the pharmacology of tachykinins in the nucleus of the solitary tract (NST) and dorsal motor nucleus of the vagus (DMNV). 3 Neurones in the NST were depolarized by substance P (SP), the presumed endogenous ligand for the NK1 receptor and these effects were mimicked by the NK1 agonists, SP-O-methylester (SPOMe), GR73632 and septide; however, SP was nearly an order of magnitude less potent than the lattertwo agonists. 4 In the DMNV, SP and NK1 receptor agonists evoked similar depolarising responses but SP appeared to be more potent than in the NST and was closer in potency to the other agonists. 5 NK1-receptorantagonists blocked responses to septide and GR73632 in the NST but had little effect on responses to SP and SPOMe. In contrast, in the DMNV the NK1-receptor antagonists blocked responses to septide and GR73632 but also reduced responses to SP and SPOMe. 6 Neurokinin A (NKA) wasalmost equipotent with septide and GR73632 in depolarizing both NST and DMNV neurones but these effects were not mimicked by a specific NK2-receptor agonist. Responses to NKA were unaffected by an NK2-receptorantagonist; however, the depolarizing effects of NKA were blocked by NK1-receptor antagonists. 7 Neurones in both DMNV and NST were unaffected by the endogenous NK3-receptor ligand, neurokinin B and by a specific agonist for this site, senktide. 8 The results with NK1 receptor agonists and antagonists suggest that the septide-sensitive NK1 site isinvolved in the excitation of both NST and DMNV neurones. The 'classical' NK1 receptor may play more of a role in the DMNV and a third unknown site may be responsible for the depolarizing response to SP in theNST. The effects of NKA are best interpreted as an action at the septide-sensitive NK1 site. This raises the possibility that anti-emetic action of the NK1 antagonists may be due to blockade of NKA transmission at the septide-sensitive site.

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Documento generato il 04/04/20 alle ore 01:02:54