Purinergic receptors expressed in human skeletal muscle fibres

Purinergic receptors expressed in human skeletal muscle fibres
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DOI:
10.1007/s11302-011-9279-y
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发表时间:
2012-06-01
影响因子:
3.5
通讯作者:
Thaning, P.
Thaning, P.
中科院分区:
医学3区
文献类型:
--
作者:
Borno, A.;Ploug, T.;Thaning, P.

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嘌呤能受体存在于大多数组织中,被认为参与多种信号通路,包括神经信号传导、细胞代谢和骨骼肌微循环的局部调节。本研究旨在确定2型糖尿病患者和年龄匹配对照者骨骼肌纤维中嘌呤能受体的分布和细胞内含量。对6例2型糖尿病患者和7例年龄匹配的对照组进行股外侧肌活检。利用光镜和共聚焦显微镜在免疫标记的肌肉活检横切面上分析嘌呤能受体。受体P2Y(4)、P2Y(11)和可能的P2X(1)存在于肌纤维的细胞内或质膜中,因此被选中进行进一步的详细形态学分析。P2X(1)受体在细胞内囊泡和肌膜中表达。肌膜中存在P2Y(4)受体。P2Y(11)受体在细胞内大量和弥漫性表达,并且在I型纤维中比在II型纤维中更明确表达,而P2X(1)和P2Y(4)没有纤维类型特异性。糖尿病患者和健康对照组的受体分布相似。目前的研究表明,嘌呤能受体位于人体骨骼肌纤维的细胞内。在健康和糖尿病受试者中相似的受体细胞定位表明糖尿病与骨骼肌纤维中嘌呤能受体分布的改变无关。我们推测嘌呤能受体的细胞内定位可能反映了肌肉代谢的调节作用;然而,需要进一步的研究来确定嘌呤能系统在骨骼肌细胞中的功能。
Purinergic receptors are present in most tissues and thought to be involved in various signalling pathways, including neural signalling, cell metabolism and local regulation of the microcirculation in skeletal muscles. The present study aims to determine the distribution and intracellular content of purinergic receptors in skeletal muscle fibres in patients with type 2 diabetes and age-matched controls. Muscle biopsies from vastus lateralis were obtained from six type 2 diabetic patients and seven age-matched controls. Purinergic receptors were analysed using light and confocal microscopy in immunolabelled transverse sections of muscle biopsies. The receptors P2Y(4), P2Y(11) and likely P2X(1) were present intracellularly or in the plasma membrane of muscle fibres and were thus selected for further detailed morphological analysis. P2X(1) receptors were expressed in intracellular vesicles and sarcolemma. P2Y(4) receptors were present in sarcolemma. P2Y(11) receptors were abundantly and diffusely expressed intracellularly and were more explicitly expressed in type I than in type II fibres, whereas P2X(1) and P2Y(4) showed no fibre-type specificity. Both diabetic patients and healthy controls showed similar distribution of receptors. The current study demonstrates that purinergic receptors are located intracellularly in human skeletal muscle fibres. The similar cellular localization of receptors in healthy and diabetic subjects suggests that diabetes is not associated with an altered distribution of purinergic receptors in skeletal muscle fibres. We speculate that the intracellular localization of purinergic receptors may reflect a role in regulation of muscle metabolism; further studies are nevertheless needed to determine the function of the purinergic system in skeletal muscle cells.