Comparison of contractions of the smooth muscle of the guinea-pig vas deferens induced by ATP and related nucleotides.
Comparison of contractions of the smooth muscle of the guinea-pig vas deferens induced by ATP and related nucleotides.
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ATP及相关核苷酸诱导豚鼠输精管平滑肌收缩的比较。
DOI：
10.1016/0014-2999(82)90437-x
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发表时间：
1982
影响因子：
5
通讯作者：
O'Donnell,JP
中科院分区：
文献类型：
--
作者：
Fedan,JS;Hogaboom,GK;Westfall,DP;O'Donnell,JP
当ATP浓度从10−7 ~ 10−2M增加时，离体豚鼠输精管收缩反应的形状发生变化。ATP浓度-响应曲线为双峰曲线，反映了响应曲线的变化。最初的性质是峰状的（10−7−3 × 10−5M），在过渡性ATP浓度（大于或等于3 × 10−5M）下，收缩获得二次的、较慢的紧缩性阶段。在高ATP浓度（10−2M）下，次级相占主导地位。为了确定这些复杂效应是否存在结构要求，将ATP的反应与含有磷酸链、核糖和腺嘌呤修饰的类似物引起的反应进行了比较。一般来说，用亚甲基或亚胺取代5 ' -酸酐键可以在低浓度下延长反应时间，但在高浓度下则可以增强或缩短反应时间。ATPγS是一种磷酸水解酶的底物，它能吸收磷酸盐，但不太能去除硫代磷酸盐，产生的反应具有极大延长的强直期。去除ATP的2′-羟基导致低浓度下的效力降低，而去除3′-羟基则没有效果。腺嘌呤1位和n6位的修饰大大降低了激动剂的活性。10−5M吲哚美辛对ATP和β， γ-亚甲基同系物的反应没有影响。结果表明，ATP与受体的多种简单相互作用参与了ATP反应的产生。在讨论的几个假设中，我们倾向于认为对低浓度ATP的阶段性反应是由受体介导并由组织酶修饰的，而对高浓度ATP的阶段性反应部分是由水解本身介导的。该假说认为构象偏好也可能存在，但仅针对输精管提出。
The shape of contractile responses of the isolated guinea-pig vas deferens changes as ATP concentration is increased from 10−7to 10−2M. The ATP concentration-response curve is bimodal and reflects the change in response profile. Initially spike-like (10−7−3 × 10−5M) in nature, contractions acquire a secondary, slower tonic phase in transitional ATP concentrations (⩾ 3 × 10−5M). At high ATP concentrations (10−2M) the secondary phase predominates. To determine if there are structural requirements for these complex effects, responses to ATP were compared to those elicited with analogs containing phosphate-chain, ribose and adenine modifications. In general, substitution of 5′-anhydride linkages with methylene or imido bridges prolonged responses to low concentrations but at high concentrations both potentiated and abbreviated the responses. ATPγS, a substrate for phosphohydrolases which incorporate phosphate but which are less able to remove thiophosphate, produced responses with a greatly prolonged tonic phase. Removal of the 2′-hydroxyl of ATP resulted in reduced potency at low concentrations while removal of the 3′-hydroxyl was without effect. Modification of both the 1 and N6positions of adenine substantially reduced agonist activity. Responses to ATP and the β, γ-methylene congener were unaffected by treatment with 10−5M indomethacin. The results indicate that more than one simple interaction of ATP with a receptor is involved in the production of responses to ATP. Of several hypotheses discussed, we favor one which suggests that the phasic responses to low concentrations of ATP are receptor-mediated and modified by tissue enzymes, while those to high concentrations are mediated, in part, by hydrolysis per se. The hypothesis, which realizes that conformational preferences may exist as well, is proposed for the vas deferens only.