5‐HT4 receptors mediating enhancement of contractility in canine stomach; an in vitro and in vivo study
5‐HT4 receptors mediating enhancement of contractility in canine stomach; an in vitro and in vivo study
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5-HT4 受体介导犬胃收缩性增强；体外和体内研究
DOI：
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
J. Schuurkes
中科院分区：
文献类型：
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作者：
N. H. Prins;A. V. D. Grijn;R. Lefebvre;L. Akkermans;J. Schuurkes
我们的目的是在体内和体外研究5-HT 4受体在犬胃收缩中的作用。在麻醉的比格犬中，选择性5-HT 4受体激动剂普卢卡必利（i. v.）在等压条件下诱导剂量依赖性紧张性胃收缩，该作用可被选择性5-HT 4受体拮抗剂GR 125487（10 μg kg−1，i. v.）拮抗。 体纵肌条的电场刺激（EFS）导致阿托品和河豚毒素敏感性收缩（L-NOARG（0.1 mM）存在于所有器官浴溶液中）。 普卢卡必利增加了这些收缩（单次给药（0.3 μM）后的最大反应：初始值的165%，或累积给药后：188%）。 在存在麦角新碱（3 μM）的情况下，5-HT也增加了EFS-收缩（单次给药（0.3 μM）后：增加至192%，累积给药后：148%）。 选择性5-HT 4受体拮抗剂GR 113808（0.1 μM）或GR 125487（10 nM）可拮抗普卢卡必利（0.3 μM）诱导的收缩增量。 当EFS诱导的收缩被阿托品或河豚毒素阻断时，普卢卡必利无效。在存在麦角新碱（3 μM）的情况下，GR 113808（0.1 μM）可阻止收缩增加至5-HT（0.3 μ M）。 普卢卡必利曲线（pEC 50 7.9）向右平行移动GR 113808 3 nM（pA 2 9.4）。 在存在麦角新碱（3 μM）的情况下，GR 113808竞争性拮抗5-HT曲线（pEC 50 8.1），产生的Schild斜率为0.8±0.2（pKB为9.1，单位Schild斜率）。 在环状体肌条中，GR 113808（0.1 μM）（124%）也阻止了普卢卡必利（0.3 μ M）诱导的EFS收缩增强（258%）。 总之，5-HT 4受体激动剂对体内近端胃运动活动的影响可以通过对胃肌壁内胆碱能神经上的5-HT 4受体的影响来解释。
We aimed to study 5‐HT4 receptors in canine stomach contractility both in vivo and in vitro. In anaesthetized Beagle dogs, the selective 5‐HT4 receptor agonist prucalopride (i.v.) induced dose‐dependent tonic stomach contractions under isobaric conditions, an effect that was antagonized by the selective 5‐HT4 receptor antagonist GR 125487 (10 μg kg−1, i.v.). Electrical field stimulation (EFS) of corpus longitudinal muscle strips resulted in atropine‐ and tetrodotoxin‐sensitive contractions (L‐NOARG (0.1 mM) present in all organ bath solutions). Prucalopride increased these contractions (maximal response after single‐dose addition (0.3 μM): 165% of initial value, or after cumulative addition: 188%). In the presence of methysergide (3 μM), 5‐HT also increased EFS‐contractions (after single‐dose addition (0.3 μM): increase to 192%, after cumulative addition: 148%). The selective 5‐HT4 receptor antagonists GR 113808 (0.1 μM) or GR 125487 (10 nM) antagonized the prucalopride (0.3 μM)‐induced contraction increments. When EFS‐induced contractions were blocked by atropine or tetrodotoxin, prucalopride was ineffective. In the presence of methysergide (3 μM), the contraction increases to 5‐HT (0.3 μM) were prevented by GR 113808 (0.1 μM). The prucalopride curve (pEC50 7.9) was shifted in parallel to the right by GR 113808 3 nM (pA2 9.4). In the presence of methysergide (3 μM), the curve to 5‐HT (pEC50 8.1) was competitively antagonized by GR 113808, yielding a Schild slope of 0.8±0.2 (pKB of 9.1 with unit Schild slope). In corpus circular muscle strips, the prucalopride (0.3 μM)‐induced augmentation of EFS‐contractions (258%) was also prevented by GR 113808 (0.1 μM) (124%). In conclusion, the effects of 5‐HT4 receptor agonists on proximal stomach motor activity in vivo can be explained by an effect on 5‐HT4 receptors on cholinergic nerves within the gastric muscle wall.
影响因子：
3.1
作者：
Heppell,J;Taylor,BM;Kelly,KA
通讯作者：
Kelly,KA