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速激肽NK(2)受体剪接变体的鉴定及其在人和大鼠组织中的表达。

Identification of a tachykinin NK(2) receptor splice variant and its expression in human and rat tissues.

作者信息

Candenas M Luz, Cintado Cristina G, Pennefather Jocelyn N, Pereda M Teresa, Loizaga Juan M, Maggi Carlo Alberto, Pinto Francisco M

机构信息

Centro de Investigaciones Cienti;ficas Isla de La Cartuja, Instituto de Investigaciones Químicas, Avda. Americo Vespucio s/n, 41092 Sevilla, Spain.

出版信息

Life Sci. 2002 Dec 6;72(3):269-77. doi: 10.1016/s0024-3205(02)02240-3.

Abstract

The tachykinins substance P, neurokinin A and neurokinin B are implicated in different diseases and play an important role in neuroimmunomodulation. These peptides interact with three distinct types of tachykinin receptors termed NK(1), NK(2) and NK(3). While most mammalian genes encoding G protein-coupling cell membrane receptors are intron-less, the three tachykinin receptors contain introns in their genomic structures. In the present study, we have identified a splice variant of the tachykinin NK(2) receptor that results from skipping of exon 2 in the processing of the tachykinin NK(2) receptor mRNA. By using reverse transcription-polymerase chain reaction analysis, we observed that the tachykinin NK(2) receptor splice variant, that we named NK(2)beta, appeared in different human and rat tissues that also express the wild type, tachykinin NK(2)alpha isoform. Compared to tachykinin receptor NK(2)alpha isoform mRNA levels, the NK(2)beta isoform was strongly expressed in human and rat uteri, expressed in a moderate degree in the rat urinary bladder, colon, duodenum and stomach and unexpressed in the rat cerebral cortex, kidney, thoracic aorta, skeletal muscle and heart. These data describe the first known tachykinin receptor splice variant and suggest that the variety of tachykinin receptors may be further expanded through the generation of splicing isoforms. The presence of the truncated isoform may have a physiological significance in the regulation of tachykinin NK(2) receptor protein levels.

摘要

速激肽P物质、神经激肽A和神经激肽B与多种疾病相关,在神经免疫调节中发挥重要作用。这些肽与三种不同类型的速激肽受体相互作用,分别称为NK(1)、NK(2)和NK(3)。虽然大多数编码G蛋白偶联细胞膜受体的哺乳动物基因没有内含子,但三种速激肽受体的基因组结构中含有内含子。在本研究中,我们鉴定出一种速激肽NK(2)受体的剪接变体,它是由速激肽NK(2)受体mRNA加工过程中外显子2的跳跃产生的。通过逆转录-聚合酶链反应分析,我们观察到我们命名为NK(2)β的速激肽NK(2)受体剪接变体出现在不同的人类和大鼠组织中,这些组织也表达野生型速激肽NK(2)α异构体。与速激肽受体NK(2)α异构体mRNA水平相比,NK(2)β异构体在人类和大鼠子宫中强烈表达,在大鼠膀胱、结肠、十二指肠和胃中中度表达,在大鼠大脑皮层、肾脏、胸主动脉、骨骼肌和心脏中未表达。这些数据描述了首个已知的速激肽受体剪接变体,并表明速激肽受体的多样性可能通过剪接异构体的产生而进一步扩大。截短异构体的存在可能在速激肽NK(2)受体蛋白水平的调节中具有生理意义。

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