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Titolo:
Serotonin reuptake inhibitor, fluoxetine, dilates isolated skeletal musclearterioles. Possible role of altered Ca2+ sensitivity
Autore:
Pacher, P; Ungvari, Z; Kecskemeti, V; Koller, A;
Indirizzi:
New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA New York Med CollValhalla NY USA 10595 t Physiol, Valhalla, NY 10595 USA Semmelweis Univ Med, Inst Pathophysiol, H-1445 Budapest, Hungary Semmelweis Univ Med Budapest Hungary H-1445 ol, H-1445 Budapest, Hungary Semmelweis Univ Med, Dept Pharmacol, H-1445 Budapest, Hungary Semmelweis Univ Med Budapest Hungary H-1445 ol, H-1445 Budapest, Hungary
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 3, volume: 127, anno: 1999,
pagine: 740 - 746
SICI:
0007-1188(199906)127:3<740:SRIFDI>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRICYCLIC ANTIDEPRESSANTS; ORTHOSTATIC HYPOTENSION; PLASMA-CONCENTRATIONS; INDUCED BRADYCARDIA; HUMAN BRAIN; NORFLUOXETINE; SERUM; HYDROCHLORIDE; OVERDOSE; CHANNELS;
Keywords:
fluoxetine (Prozac); dilation; endothelium; arteriolar potassium channels; 5-hydroxytryptamine; Ca2+ sensitivity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Koller, A New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA New YorkMed Coll Valhalla NY USA 10595 Valhalla, NY 10595 USA
Citazione:
P. Pacher et al., "Serotonin reuptake inhibitor, fluoxetine, dilates isolated skeletal musclearterioles. Possible role of altered Ca2+ sensitivity", BR J PHARM, 127(3), 1999, pp. 740-746

Abstract

1 Inhibitors of serotonin reuptake in the central nervous system, such as fluoxetine, may also affect the function of vascular tissues. Thus, we investigated the effect of fluoxetine on the vasomotor responses of isolated, pressurized arterioles of rat gracilis muscle (98 +/- 4 mu m in diameter at 80 mmHg perfusion pressure).2 We have found that increasing concentrations of fluoxetine dilated arterioles up to 155 +/- 5 mu m with an EC50 of 2.5 +/- 0.5 x 10(-6) M.3 Removal of the endothelium, application of 4-aminopyridine (4-AP, an inhibitor of aminopyridine sensitive K+ channels), or use of glibenclamide (aninhibitor of ATP-sensitive K+ channels) did not affect the vasodilator response to fluoxetine.4 In the presence of 10(-6), 2 x 10(-6) or 10(-5) M fluoxetine noradrenaline (NA, 10(-9)-10(-5) M) and 5-hydroxytryptamine (5-MT, 10(-9)-10(-5) M)-induced constrictions were significantly attenuated resulting in concentration-dependent parallel rightward shifts of their dose-response curves (pA(2) = 6.1 +/- 0.1 and 6.9 +/- 0.1, respectively).5 Increasing concentrations of Ca2+ (10(-4)-3 x 10(-2) M) elicited arteriolar constrictions (up to similar to 30%), which were markedly reduced by 2x10(-6) M fluoxetine, whereas 10(-5) M fluoxetine practically abolished these responses.6 In conclusion, fluoxetine elicits substantial dilations of isolated skeletal muscle arterioles, a response which is not mediated by 4-AP- and ATP-sensitive Ki channels or endothelium-derived dilator factors. The findings that fluoxetine had a greater inhibitory effect on Ca2+ elicited constrictions than on responses to NA and 5-HT suggest that fluoxetine may inhibit Ca2 channel(s) or interfere with the signal transduction by Ca2+ in the vascular smooth muscle cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 12:23:02