Effect of Kil769, a Novel K+-channel Opener, on Sensitivity to Ca2+ of Contractile Elements and Inositol Phosphate Formation in Porcine Coronary Artery

3区 · 医学

Article

作者: Izawa, Toshio ; Yokoyama, Takashi ; Okada, Yuji ; Izumi, Hideakira ; Kasai, Hideo ; Ogawa, Nobuyuki

Abstract:

To determine whether Kil769, a novel K+-channel opener, acts intracellularly in vasorelaxation, we compared the effects of Kil 769 on force of contraction, intracellular Ca2+ concentration ([Ca2+]i) and inositol phosphate (IP1) formation with those of Ca2+-channel blockers in isolated porcine coronary artery.Kil 769 (10 μm) and verapamil (1 μm), which produced submaximal relaxation, reduced the increase in [Ca2+]i and force of contraction induced by 25 mM KC1. Verapamil reduced [Ca2+]i and the force of contraction to a similar extent but Kil 769 reduced force of contraction more strongly than it did [Ca2+]i. Kil 769 also inhibited U46619 (9,11-dideoxy-9α, 11α-methano-epoxy-PGF2a)-induced IP1 formation and glibenclamide blocked its inhibitory effect.These results suggest that the opening of K+ channels induced by Kil 769 reduces the Ca2+ sensitivity of contractile elements and inositol phospholipid hydrolysis which is related to the Ca2+ release from intracellular storage.

1994-09-01·General pharmacology

Comparative analysis of vasodilating Mechanisms of Kil769, Ki3315 and KRN2391, pyridinecarboximidamide derivatives, in porcine isolated coronary artery

Article

作者: Izawa, Toshio ; Yokoyama, Takashi ; Okada, Yuji ; Jinno, Yasuhiro ; Izumi, Hideakira ; Ogawa, Nobuyuki

1. The vasodilating mechanisms of pyridinecarboximidamide derivatives which have a nitroxyl group (KRN2391), a phenyl group (Ki1769) or a hydroxyl group (Ki3315) were studied in porcine isolated coronary artery. 2. KRN2391 (10(-6) M) increased cyclic GMP formation but did not affect intracellular cyclic AMP level. Ki1769 (10(-5) M) and Ki3315 (10(-3) M) had no effect on intracellular cyclic GMP and cyclic AMP levels. 3. Despite producing submaximal relaxation at KRN2391 (10(-6) M) and nitroglycerin (10(-6) M), the increase in cyclic GMP caused by KRN2391 was lower than that caused by nitroglycerin. 4. Methylene blue (10(-5) M) inhibited KRN2391- and nitroglycerin-induced relaxations but did not affect Ki1769- and Ki3315-induced relaxation. 5. Glibenclamide (10(-6) M) inhibited KRN2391-, Ki1769- and Ki3315-induced relaxation but did not affect nitroglycerin-induced relaxation. 6. These results suggest that the nitroxyl group of KRN239 contributes to its nitrate action and the pyridinecarboximidamide moiety plays an important role of developing a K channel opening action.

100 项与 KIL-769 相关的药物交易

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