UTP induces vascular responses in the isolated and perfused canine epicardial coronary artery via UTP‐preferring P2Y receptors
UTP induces vascular responses in the isolated and perfused canine epicardial coronary artery via UTP‐preferring P2Y receptors
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UTP 通过 UTP 偏好的 P2Y 受体在分离和灌注的犬心外膜冠状动脉中诱导血管反应
DOI：
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发表时间：
1997
影响因子：
7.3
通讯作者：
S. Chiba
中科院分区：
文献类型：
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作者：
Takako Matsumoto;T. Nakane;S. Chiba
1 对分离和灌注的犬心外膜冠状动脉对尿苷 5'-三磷酸 (UTP) 的血管收缩反应进行药理学分析。 2 在基础灌注压下，UTP 以剂量相关的方式引起血管收缩，并且大剂量（超过 10nmol）时，血管收缩有时会导致轻微的血管舒张。血管收缩效力的顺序为UTP=UDP>ATP>TTPITP>>UMP。当灌注压升高 20mm KCl 时，血管收缩没有改变，大剂量时会引起轻微的血管舒张。大剂量诱导血管舒张效力的排序。血管舒张效力的顺序为ATP>>ITPUDP>UTPTTP。对 UTP 的最大血管舒张反应远小于对 ATP 的最大血管舒张反应。 UMP 不引起血管舒张。 3 P2X 受体激动剂和脱敏剂 α,β-亚甲基 ATP (1 μm) 和 P2 受体拮抗剂苏拉明 (100 μm) 抑制对 ATP 的血管收缩反应，但不抑制对 UTP 和 UDP 的血管收缩反应。 P2 受体拮抗剂活性蓝 2 (30 μm) 不会抑制血管对 UTP 的反应。 4 UTP (200 μm) 使血管收缩剂对 UTP 的反应脱敏，但不会使血管舒张剂对 UTP 的反应或血管收缩剂对 ATP 和 UDP 的反应脱敏。 UDP (200 μm) 不会降低血管对 UTP 的反应。 5 用己糖激酶（分别为 10 和 1 uml−1）预孵育 UDP 储备液和动脉制剂不会改变血管收缩剂对 UDP 的反应。 6 Ca 通道阻滞剂地尔硫卓 (1 μm) 抑制对 UTP 的血管收缩反应，但不抑制对 ATP 和 UDP 的血管收缩反应。在含有 1mm EGTA 的无 Ca2+ 溶液中孵育可抑制血管对 ATP、UTP 和 UDP 的反应。 7 通过腔内注射皂苷（1 mg）去除内皮细胞抑制了对 UTP 的血管舒张反应。环加氧酶抑制剂吲哚美辛 (1 μm) 抑制对 UTP 的血管舒张反应，但一氧化氮合酶抑制剂 NG-硝基-L-精氨酸 (300 μm) 没有抑制作用。 8 结果表明，(1) UTP 通过平滑肌上 UTP 偏好的 P2Y 受体诱导血管收缩，并通过与介导 UTP 诱导血管收缩和介导内皮上 ATP 介导血管舒张的受体不同的受体诱导血管舒张，主要通过犬心外膜冠状动脉中前列环素的释放； (2) UDP通过UDP偏好的P2Y受体诱导血管收缩； (3) L型Ca离子通道参与UTP引起的血管收缩，但不参与UDP引起的血管收缩。
1 Vasoconstrictor responses of the isolated and perfused canine epicardial coronary artery to uridine 5′‐triphosphate (UTP) were analysed pharmacologically. 2 At basal perfusion pressure, UTP induced vasoconstriction in a dose‐related manner and the vasoconstriction was sometimes followed by a slight vasodilatation at large doses (more than 10 nmol). The rank order of potency for vasoconstriction was UTP=UDP>ATP>TTPITP>> UMP. At raised perfusion pressure by 20 mm KCl, the vasoconstriction was not changed and a small vasodilatation was induced at large doses. The rank order of potency for vasodilatation was induced at large doses. The rank order of potency for vasodilatation was ATP>>ITPUDP>UTPTTP. The maximal vasodilator response to UTP was much less than that to ATP. UMP did not induce vasodilatation. 3 The P2X receptor agonist and desensitizing agent α,β‐methylene ATP (1 μm) and the P2 receptor antagonist suramin (100 μm) inhibited the vasoconstrictor responses to ATP but not those to UTP and UDP. The P2 receptor antagonist reactive blue 2 (30 μm) did not inhibit the vascular responses to UTP. 4 UTP (200 μm) desensitized the vasoconstrictor responses to UTP, but not either the vasodilator responses to UTP or the vasoconstrictor responses to ATP and UDP. UDP (200 μm) did not desensitize the vascular responses to UTP. 5 Preincubating the UDP stock solution and arterial preparation with hexokinase (10 and 1 uml−1, respectively) did not change the vasoconstrictor responses to UDP. 6 The Ca channel blocker diltiazem (1 μm) inhibited the vasoconstrictor responses to UTP but not those to ATP and UDP. Incubation in a Ca2+‐free solution containing 1 mm EGTA inhibited the vascular responses to ATP, UTP and UDP. 7 Removal of the endothelium by an intraluminal injection of saponin (1 mg) inhibited the vasodilator responses to UTP. Indomethacin, a cyclo‐oxygenase inhibitor (1 μm), inhibited the vasodilator responses to UTP, but NG‐nitro‐l‐arginine, a nitric oxide synthase inhibitor (300 μm), did not have an inhibitory effect. 8 The results suggest that (1) UTP induces vasoconstriction via UTP‐preferring P2Y receptors on the smooth muscle and vasodilatation via receptors different from those mediating the vasoconstriction induced by UTP and mediating the vasodilatation by ATP on the endothelium, through mainly the release of prostacyclin in the canine epicardial coronary artery; (2) UDP induces vasoconstriction via UDP‐preferring P2Y receptors; and (3) L‐type Ca ion channels are involved in the vasoconstriction induced by UTP, but not in that induced by UDP.
三种磷脂酶 C 激活 P2 受体的尿苷核苷酸选择性：鉴定 UDP 选择性、UTP 选择性以及 ATP 和 UTP 特异性受体。
DOI：
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发表时间：
1996
期刊：
Molecular pharmacology.
影响因子：
--
作者：
Nicholas,RA;Watt,WC;Lazarowski,ER;Li,Q;Harden,K
通讯作者：
Harden,K
影响因子：
13.8
作者：
Fredholm, BB;Abbracchio, MP;Williams, M
通讯作者：
Williams, M