5-HT7 Receptor Restrains 5-HT-induced 5-HT2A Mediated Contraction in the Isolated Abdominal Vena Cava.
5-HT7 Receptor Restrains 5-HT-induced 5-HT2A Mediated Contraction in the Isolated Abdominal Vena Cava.
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DOI：
10.1097/fjc.0000000000001057
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发表时间：
2021-08-01
影响因子：
3
通讯作者：
Watts SW
中科院分区：
文献类型：
--
作者：
Gonzalez-Pons R;McRae K;Thompson JM;Watts SW
尽管被发现是一种血管收缩剂，但将 5-羟色胺（5-HT，血清素）注入人和啮齿动物体内可以降低血压。这主要是通过激活 5-HT7 受体以及至少部分地通过静脉舒张而发生的。发生这种情况的血管机制包括直接受体激活导致血管舒张和/或抑制收缩性 5-HT 受体激活。本研究检验了 5-HT7 受体抑制 5-HT2A 受体激活的假设。一个子假设是激动剂诱导的 5-HT7 受体激活（与组成性活性无关）是否是这种抑制所必需的。我们的模型是从正常雄性斯普拉格-道利大鼠身上分离出的腹主动脉和腔静脉。研究使用实时 PCR 和药理学方法在分离的组织浴中测量等长张力。虽然主动脉和腔静脉中的 5-HT2A 受体 mRNA 表达均显着大于 5-HT7 受体 mRNA，但腔静脉中的 5-HT7/5-HT2A 受体 mRNA 比率 (0.30) 高于主动脉 (0.067)。与对照相比，SB266970 和 DR 4458 的 5-HT7 受体拮抗作用使离体静脉中 5-HT 的最大收缩增加了 50% 以上。 5-HT2A 受体激动剂 TCB-2 和 NBOH 在主动脉中比 5-HT 更有效，但效果较差，仅作为部分激动剂。相比之下，这三种相同的激动剂在激动剂浓度高达 10 μM 的情况下不会引起从同一大鼠分离的腔静脉收缩。 SB269970 对 5-HT7 受体的拮抗作用并没有增加 TCB-2 或 NBOH 的效力或功效。这些数据支持5-HT 7 受体本身需要被刺激以减少收缩，并且在离体的腹腔静脉中5-HT 7 受体几乎没有组成性活性。
Though discovered as a vasoconstrictor, 5-hydroxytryptamine (5-HT, serotonin) infused into man and rodent reduces blood pressure. This occurs primarily through activation of 5-HT7 receptors and, at least in part, venodilation. Vascular mechanisms by which this could occur include direct receptor activation leading to vasodilation and/or suppression of contractile 5-HT receptor activation. The present study tests the hypothesis that the 5-HT7 receptor restrains activation of the 5-HT2A receptor. A sub hypothesis is whether agonist-induced activation of the 5-HT7 receptor -- independent of constitutive activity -- is necessary for this restraint. The isolated abdominal aorta and vena cava from the normal male Sprague-Dawley rat was our model. Studies used real time PCR and a pharmacological approach in the isolated tissue bath for measurement of isometric tone. While 5-HT2A receptor mRNA expression in both aorta and vena cava was significantly larger than that of the 5-HT7 receptor mRNA, the 5-HT7/5-HT2A receptor mRNA ratio was greater in the vena cava (0.30) than in the aorta (0.067). 5-HT7 receptor antagonism by SB266970 and DR 4458 increased maximum contraction to 5-HT in the isolated vein by over 50% vs control. The 5-HT2A receptor agonists TCB-2 and NBOH were more potent in the aorta compared to 5-HT but less efficacious, serving as partial agonists. By contrast, these same three agonists caused no contraction in the vena cava isolated from the same rats up to a 10 μM agonist concentration. Antagonism of the 5-HT7 receptor by SB269970 did not increase either the potency or efficacy of TCB-2 or NBOH. These data support that the 5-HT7 receptor itself needs to be stimulated to reduce contraction and that there is little constitutive activity of the 5-HT7 receptor in the isolated abdominal vena cava.