Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
MCI-154 INCREASES CA2- A STUDY USING A NOVEL IN-VITRO MOTILITY ASSAY TECHNIQUE( SENSITIVITY OF RECONSTITUTED THIN FILAMENT )
Autore:
SATA M; SUGIURA S; YAMASHITA H; FUJITA H; MOMOMURA SI; SERIZAWA T;
Indirizzi:
CASE WESTERN RESERVE UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,10900 EUCLIDAVE CLEVELAND OH 44106 UNIV TOKYO,FAC MED,DEPT INTERNAL MED 2 TOKYO 113 JAPAN
Titolo Testata:
Circulation research
fascicolo: 4, volume: 76, anno: 1995,
pagine: 626 - 633
SICI:
0009-7330(1995)76:4<626:MICASU>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
CONGESTIVE-HEART-FAILURE; CARDIOTONIC AGENT; GUINEA-PIG; HAMSTER CARDIOMYOPATHY; INORGANIC-PHOSPHATE; CONTRACTILE FAILURE; VENTRICULAR MUSCLE; CARDIAC-MUSCLE; CA++ BINDING; IN-VITRO;
Keywords:
CA2+ SENSITIZER; MYOSIN; REGULATORY PROTEINS; IN VITRO MOTILITY ASSAY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
M. Sata et al., "MCI-154 INCREASES CA2- A STUDY USING A NOVEL IN-VITRO MOTILITY ASSAY TECHNIQUE( SENSITIVITY OF RECONSTITUTED THIN FILAMENT )", Circulation research, 76(4), 1995, pp. 626-633

Abstract

MCI-154 pyridylamino)phenyl]-4,5-dihydro-3(2H)pyridazinone hydrochloride trihydrate) is a potent novel cardiotonic agent whose positive inotropism is shown to be mainly based on an increase in Ca2+ sensitivityof the contractile apparatus. To elucidate the exact mechanism through which this drug acts, we investigated the movement of the reconstituted thin filament on a myosin layer in vitro. Cardiac thin filaments were reconstituted from actin and tropomyosin-troponin complex purifiedfrom rat cardiac acetone powder separately. Double staining of the filament showed that tropomyosin-troponin complex was integrated along actin filament homogeneously. Thin filaments thus prepared were fluorescently labeled and made to slide on rat cardiac myosin fixed on a glass coverslip while varying the [Ca2+] of the medium (control, pH 7.2 at25 degrees C). When [Ca2+] was low, the filaments showed only brownian motion. However, above a certain level of [Ca2+] (the threshold [Ca2]), the filaments started to slide, and the velocity increased, reaching the maximum velocity within a very narrow range of [Ca2+]. The regulation was completely abolished by using simple actin filaments without tropomyosin-troponin complex, demonstrating that the regulatory proteins are responsible for this Ca2+ regulation of the movement of the reconstituted thin filament. Under the control condition, addition of MCI-154 shifted the threshold [Ca2+] to a lower level (sensitization) in a concentration-related manner. And 10(-4) mol/L of MCI-154 reversed the desensitization effect induced by either acidosis (pH 6.8), low temperature (15 degrees C), or the addition of inorganic phosphate (10mmol/L). However, the maximum sliding Velocity was not affected by the drug under any condition. In conclusion, MCI-154 directly sensitizedthe contractile apparatus under not only physiological but also pathophysiological conditions. This in vitro motility assay technique usingreconstituted thin filaments is a useful tool for studying the mechanism of action of Ca2+ sensitizers.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 20:00:38