The toadfish serotonin 2A (5-HT2A) receptor: molecular characterization and its potential role in urea excretion
The toadfish serotonin 2A (5-HT2A) receptor: molecular characterization and its potential role in urea excretion
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DOI：
10.1016/j.cbpa.2012.07.013
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发表时间：
2012-11-01
影响因子：
2.3
通讯作者：
McDonald, M. Danielle
中科院分区：
文献类型：
--
作者：
Mager, Edward M.;Medeiros, Lea R.;McDonald, M. Danielle
基于早期药理工作，5-羟色胺2A （5-HT2A）受体亚型被认为参与了蟾鱼脉动性尿素排泄的调节。以下研究的目的是在分子水平上表征蟾鱼5-HT2A受体，确定该受体主要表达的组织，并通过检测5-HT2A受体拮抗剂酮色林对静息脉冲性尿素排泄率的影响，进一步研究蟾鱼脉动性尿素排泄的药物学特异性。全长蟾鱼5-HT2A受体编码496个氨基酸序列，与其他生物的5-HT2A受体具有57-80%的序列同源性，在重要的配体结合残基上具有100%的保守性。蟾鱼5-HT2A受体mRNA在鱼鳔和性腺的表达量最高，其次是全脑。所有其他组织（食道、胃、前肠、后肠、直肠、肝、肾、心脏、肌肉和鳃）的mRNA表达水平显著低于全脑。脑内5-HT2A受体mRNA在后脑、端脑和中脑/间脑区表达量最高。用5-HT2A受体拮抗剂酮色林治疗，由于尿素脉冲大小减少而脉冲频率无显著变化，导致自发尿素排泄的脉动成分显著降低。这些结果进一步支持了5-HT2A受体在调节蟾蜍搏动性尿素排泄中的作用。(C) 2012爱思唯尔公司版权所有。
Based on early pharmacological work, the serotonin 2A (5-HT2A) receptor subtype is believed to be involved in the regulation of toadfish pulsatile urea excretion. The goal of the following study was to characterize the toadfish 5-HT2A receptor at a molecular level, to determine the tissues in which this receptor is predominantly expressed and to further investigate the pharmacological specificity of toadfish pulsatile urea excretion by examining the effect of ketanserin, a 5-HT2A receptor antagonist, on resting rates of pulsatile urea excretion. The full-length toadfish 5-HT2A receptor encodes a 496 amino acid sequence and shares 57-80% sequence identity to 5-HT2A receptors of other organisms, with 100% conservation among important ligand-binding residues. Toadfish 5-HT2A receptor mRNA expression was highest in the swim bladder and gonad, followed by the whole brain. All other tissues tested (esophagus, stomach, anterior intestine, posterior intestine, rectum, liver, kidney, heart, muscle and gill) had mRNA expression levels that were significantly less than whole brain. Toadfish 5-HT2A receptor mRNA expression within the brain was highest in the hindbrain, telencephalon and midbrain/diencephalon regions. Treatment with the 5-HT2A receptor antagonist, ketanserin, resulted in a significant decrease in the pulsatile component of spontaneous urea excretion due to a reduction in urea pulse size with no significant change in pulse frequency. These results lend further support for the 5-HT2A receptor in the regulation of pulsatile urea excretion in toadfish. (C) 2012 Elsevier Inc. All rights reserved.