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Titolo:
INHIBITION OF SYMPATHETIC NORADRENERGIC TRANSMISSION BY GUANABENZ ANDGUANETHIDINE IN RAT ISOLATED MESENTERIC-ARTERY - INVOLVEMENT OF NEURONAL POTASSIUM CHANNELS
Autore:
FABIANI ME; STORY DF;
Indirizzi:
RMIT UNIV,FAC BIOMED & HLTH SCI,DEPT MED LAB SCI,PHARMACOL RES GRP,GPO BOX 2476V MELBOURNE VIC 3001 AUSTRALIA
Titolo Testata:
Pharmacological research
fascicolo: 3, volume: 33, anno: 1996,
pagine: 171 - 180
SICI:
1043-6618(1996)33:3<171:IOSNTB>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
VAS-DEFERENS; RABBIT ATRIA; APAMIN; NORADRENALINE; CONDUCTANCE; MECHANISM; WY-8678; EFFLUX; SODIUM;
Keywords:
GUANABENZ; GUANETHIDINE; POTASSIUM CHANNELS; NORADRENERGIC TRANSMISSION; TRANSMITTER NORADRENALINE RELEASE; RAT MESENTERIC ARTERY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
M.E. Fabiani e D.F. Story, "INHIBITION OF SYMPATHETIC NORADRENERGIC TRANSMISSION BY GUANABENZ ANDGUANETHIDINE IN RAT ISOLATED MESENTERIC-ARTERY - INVOLVEMENT OF NEURONAL POTASSIUM CHANNELS", Pharmacological research, 33(3), 1996, pp. 171-180

Abstract

The present study investigated the effects of the alpha(2)-adrenoceptor agonist guanabenz and the adrenergic neurone blocking drug guanethidine on the resting and stimulation-induced (S-I) effluxes of radioactivity from rat isolated mesenteric artery preparations in which the noradrenergic transmitter stores had been radiolabelled with [H-3]-noradrenaline, The efflux of radioactivity evoked by electrical field stimulation of periarterial sympathetic nerves (60 s trains of 1 ms pulses,2 Hz, 12 V) was taken as an index of transmitter noradrenaline release. Guanabenz (0.1-10 mu M) decreased, in a concentration-dependent manner, both the resting and S-I effluxes of radioactivity, Guanethidine (0.1 and 1 mu M) also decreased S-I efflux but increased resting efflux, both effects being concentration dependent. The inhibitory effects of guanabenz on both resting and S-I effluxes were reduced by blockadeof the neuronal amine carrier with desipramine (1 mu M). The inhibitory effect of guanabenz on resting efflux was prevented by inhibition of monoamine oxidase with pargyline (100 mu M). The inhibitory effect of guanabenz on S-I efflux was not due to activation of prejunctional alpha(2)-adrenoceptors since the inhibition was not blocked by the selective alpha(2)-adrenoceptor antagonist idazoxan (0.1 mu M). However, the inhibitory effect of guanabenz and guanethidine on S-I efflux was reduced by the inhibitor of Ca2+-activated potassium channels apamin (0.1 mu M). The findings suggest that guanabenz, like guanethidine, enters noradrenergic nerve terminals by the neuronal amine carrier, The inhibition of resting efflux produced by guanabenz may be due to inhibition of neuronal monoamine oxidase. The enhancement of resting efflux produced by guanethidine is attributable to its indirect sympathomimetic action. Finally, guanabenz and guanethidine may inhibit transmitter noradrenaline release by activating potassium channels on sympathetic noradrenergic nerve terminals, These findings may be relevant to the mechanism of adrenergic neurone blockade. (C) 1996 The Italian Pharmacological Society

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/09/20 alle ore 05:39:13