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• W2003498691 abstract "This study was designed to determine if 4-aminopyridine, a reported inhibitor of the transient outward K + current ( I to ), alters the inotropic actions elicited via stimulation of WB4101- or chloroethylclonidine-sensitive receptors in rat myocardium. WB4101 ( N -[2-(2,6-dimethoxyphenoxy)ethyl]-2,3-dihydro-1,4-benzodioxin-2-methanamine) is a competitive antagonist that is selective for α 1A - and α 1C -adrenoceptors, while chloroethylclonidine is an irreversible blocker that is reported to antagonize α 1B -, α 1C -, and α 1D -adrenoceptor binding. Inotropic effects of the α 1 -adrenoceptor agonist phenylephrine were examined in isolated left atrial and papillary muscle before and after addition of 4-aminopyridine, and before and after addition of 4-aminopyridine in preparations pretreated with chloroethylclonidine or WB4101. In addition, effects of phenylephrine were examined before and after treatment with staurosporine (an inhibitor of protein kinase C) in chloroethylclonidine-pretreated preparations. Phenylephrine (10 μM) elicited a sustained positive inotropic response in left atria and a triphasic inotropic action in papillary muscle (transient positive and negative inotropic components preceding a sustained positive inotropic response). 4-Aminopyridine (1.0, 1.7, 3.0 mM) reduced the sustained positive inotropic responses in the absence of antagonists and in chloroethylclonidine-pretreated preparations. However, in the presence of 10 nM WB4101, 4-aminopyridine had no effect on the remaining inotropic actions of phenylephrine. The sustained positive inotropic response to the α 1 -agonist in chloroethylclonidine-pretreated preparations was not inhibited by 100 nM staurosporine. These data suggest that the sustained positive inotropic actions of α 1A -adrenoceptor stimulation in rat atrial and ventricular myocardium are mediated via non-protein kinase C-associated reductions in I to ." @default.
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• W2003498691 date "1996-05-01" @default.
• W2003498691 modified "2023-09-26" @default.
• W2003498691 title "The positive inotropic effect of α1A-adrenoceptor stimulation is inhibited by 4-aminopyridine" @default.
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• W2003498691 doi "https://doi.org/10.1016/0014-2999(96)00132-x" @default.
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