کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2534672 1559090 2009 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dual action of AJG049, a novel gut selective Ca2+ channel antagonist, on Ba2+ currents and contractions in guinea-pig antrum myocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Dual action of AJG049, a novel gut selective Ca2+ channel antagonist, on Ba2+ currents and contractions in guinea-pig antrum myocytes
چکیده انگلیسی

Ca2+ channel antagonists are useful to reduce the abnormal motility in patients with irritable bowel syndrome. We have therefore examined the effects of a newly synthesized antagonist AJG049, on voltage-dependent L-type Ca2+ channels in gastric antrum. Intracellular recordings were made from sheets of the circular muscle layer of guinea-pig gastric antrum, with simultaneous measurement of spontaneous contraction activity, and the effects of AJG049 were studied. The effects of AJG049 on voltage-dependent Ba2+ currents (IBa) and the basal membrane currents at − 70 mV in dispersed smooth muscle cells were also investigated by the use of conventional whole-cell patch-clamp techniques. Although AJG049 (100 nM) enhanced the peak amplitude of spontaneous contractions, high concentrations (≥ 10 µM) had inhibitory effects. In whole-cell configuration, AJG049 (10 nM) reversibly enhanced the peak amplitude of IBa in a voltage-dependent manner whilst high concentrations (≥ 100 nM) suppressed the peak amplitude in a concentration- and voltage-dependent manner. AJG049 (300 nM) caused little shift in the activation curve at a holding potential of − 70 mV although the voltage dependence of the steady-state inactivation was shifted to more negative potentials by 5 mV in its presence. AJG049 caused a delay of the recovery from the inactivated state of IBa. Furthermore, AJG049 reduced the amplitude of the basal membrane currents at − 70 mV in a concentration-dependent manner. These results suggest that AJG049 possesses a dual action on voltage-dependent Ca2+ channels in circular layer of guinea-pig antrum.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 605, Issues 1–3, 1 March 2009, Pages 138–144
نویسندگان
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