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Titolo:
Imiquimod-elicited emesis is mediated by the area postrema, but not by direct neuronal activation
Autore:
Strominger, NL; Brady, R; Gullikson, G; Carpenter, DO;
Indirizzi:
Albany Med Coll, Albany, NY 12208 USA Albany Med Coll Albany NY USA 12208Albany Med Coll, Albany, NY 12208 USA SUNY Albany, Sch Publ Hlth, Albany, NY USA SUNY Albany Albany NY USASUNY Albany, Sch Publ Hlth, Albany, NY USA 3M Pharmaceut, St Paul, MN USA 3M Pharmaceut St Paul MN USA3M Pharmaceut, St Paul, MN USA
Titolo Testata:
BRAIN RESEARCH BULLETIN
fascicolo: 3, volume: 55, anno: 2001,
pagine: 445 - 451
SICI:
0361-9230(200106)55:3<445:IEIMBT>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNE-RESPONSE MODIFIER; ALPHA-INTERFERON; SQUIRREL-MONKEY; FERRET; TRIAL; IMMUNOMODULATOR; INDUCTION; CANCER; WARTS;
Keywords:
imiquimod; interferon inducers; ablations; electrophysiology; ferrets; emesis; area postrema;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Strominger, NL Albany Med Coll, Mail Code 135,47 New Scotland Ave, Albany,NY 12208 USA Albany Med Coll Mail Code 135,47 New Scotland Ave Albany NY USA 12208
Citazione:
N.L. Strominger et al., "Imiquimod-elicited emesis is mediated by the area postrema, but not by direct neuronal activation", BRAIN RES B, 55(3), 2001, pp. 445-451

Abstract

The immunomodulator, imiquimod, has been shown to have antiviral and antitumor properties in animal models. It also has been reported to alter cytokine levels in both animals and humans. However, because imiquimod appeared to be emetic, studies were conducted to determine the degree of sensitivity,and the pathways. involved. Subcutaneous administration of greater than orequal to 10 mg/kg imiquimod to ferrets elicited emesis with latencies as short as 2 '; 12 and 15 mg/kg were optimal doses. Emetic responsiveness was eliminated by complete ablation of the area postrema, but was unaffected bybilateral supradiaphragmatic section of the vagus nerve. This indicates that the emesis is produced by an activation of the chemoreceptor trigger zone B the area postrema. Ferret brain stem slices (450 mum) were preincubatedin oxygenated Krebs-Ringer and then mounted in a submerged slice recordingchamber. Extracellular recordings of spontaneous and ionophoretically evoked activity of area postrema neurons were obtained for up to 8 h, while theeffect of bath-applied imiquimod was determined. Under control conditions,neurons showed a low frequency spontaneous discharge. Introduction of imiquimod (concentration range, 1 X 10(-7) to 5 x 10(-8) M) had no effect on neuronal firing. With ionophoresis of glutamate from an independent micropipette, a brief excitatory response was obtained. We conclude that imiquimod does not directly excite area postrema neurons. It is likely that imiquimod causes synthesis and release of some unknown emetic substance(s), very possibly cytokines. (C) 2001 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 13:16:48