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• W1967450652 abstract "Prucalopride is a selective 5-hydroxytryptamine type 4 (5-HT₄) receptor agonist developed for the treatment of gastrointestinal disorders. The endogenous agonist 5-HT acting via 5-HT₄ receptors increases the L-type Ca²⁺ current (I_CaL) with potentially proarrhythmic consequences (Pau et al., 2003). The aims of this study were to investigate the effects of prucalopride on I_CaL, action potentials, refractory period, and arrhythmic activity in human atrial myocytes, and to compare these with the effects of 5-HT, using the whole-cell perforated patch-clamp technique. Prucalopride (10^–9 to 10^–4 M) produced a concentration-dependent increase in I_CaL amplitude, with a maximum response at 10 μM, from –5.3 ± 0.6 to –10.9 ± 1.5 pA/pF (<i>p</i> < 0.05; <i>n</i> = 22 cells, 10 patients), without affecting its voltage-dependence. Subsequent application of 10 μM 5-HT further increased I_CaL to –17.7 ± 2.8 pA/pF (<i>p</i> < 0.05; <i>n</i> = 16 cells, 9 patients). The increase in I_CaL by prucalopride, 98 ± 15%, was significantly smaller than that by 5-HT, 233 ± 26% (<i>p</i> < 0.05). Prucalopride (10 μM) significantly increased the action potential duration at 50% repolarization (APD₅₀) from 12 ± 2 to 17 ± 3 ms (<i>p</i> < 0.05; <i>n</i> = 22 cells, 9 patients). Following washout of prucalopride, 5-HT (10 μM) increased APD₅₀, to a greater extent, from 14 ± 3 to 32 ± 7 ms (<i>p</i> < 0.05; <i>n</i> = 11 cells; 8 patients). The APD₇₅, APD₉₀, and effective refractory period were unaffected by prucalopride or 5-HT. Furthermore, 5-HT induced abnormal depolarizations in 27% of the cells studied, whereas prucalopride induced none (<i>p</i> < 0.05). In conclusion, in human atrial cells, prucalopride, at concentrations markedly above those used therapeutically, acted as partial agonist on I_CaL and APD₅₀, with no effect on late repolarization or refractory period, and was devoid of arrhythmic activity." @default.
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• W1967450652 date "2005-01-11" @default.
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• W1967450652 title "Electrophysiological Effects of Prucalopride, a Novel Enterokinetic Agent, on Isolated Atrial Myocytes from Patients Treated with β-Adrenoceptor Antagonists" @default.
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• W1967450652 doi "https://doi.org/10.1124/jpet.104.076869" @default.
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