Platelet-derived growth factor receptor-α-positive cells and not smooth muscle cells mediate purinergic hyperpolarization in murine colonic muscles
Platelet-derived growth factor receptor-α-positive cells and not smooth muscle cells mediate purinergic hyperpolarization in murine colonic muscles
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DOI：
10.1152/ajpcell.00080.2014
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发表时间：
2014-09-15
影响因子：
5.5
通讯作者：
Sanders, Kenton M.
中科院分区：
文献类型：
--
作者：
Kurahashi, Masaaki;Mutafova-Yambolieva, Violeta;Sanders, Kenton M.
肠抑制性神经传递是胃肠运动神经调节的重要特征。嘌呤能神经传递通过P2 Y（1）受体介导抑制性神经控制的一个阶段。几十年来，ATP一直被认为是嘌呤能神经递质，平滑肌细胞（SMC）被认为是抑制性神经传递的主要靶点。最近的实验对这两种假设提出了质疑，并建议另一种细胞类型，血小板衍生生长因子受体α阳性（PDGFR α（+））细胞，是嘌呤能神经传递的靶点。我们比较了PDGFR α（+）细胞和SMC对几种嘌呤化合物的反应，以确定这些细胞是否以与肠道抑制性神经传递一致的方式反应。ATP使PDGFR α（+）细胞超极化，但使SMC去极化。PDGFR α（+）细胞中只有部分ATP反应被MRS 2500（一种P2 Y（1）拮抗剂）阻断。ADP、MRS 2365、β-NAD和腺苷5-二磷酸核糖、P2 Y（1）激动剂、超极化PDGFR α（+）细胞，这些反应被MRS 2500阻断。5-二磷酸腺苷核糖比β-NAD更能诱发超极化反应。P2 Y（1）激动剂不能引起SMC的反应。小电导Ca 2+激活的K+通道激动剂环己基-[2-（3，5-二甲基-吡唑-1-基）-6-甲基-嘧啶-4-基]-胺在SMC中引起小超极化反应，这与这些细胞中小电导Ca 2+激活的K+通道的低表达和电流密度一致。P2 Y（1）激动剂在PDGFR α（+）细胞而非平滑肌细胞中引起的大幅度超极化反应与完整肌肉中响应嘌呤能神经传递的抑制性连接电位的产生一致。PDGFR α（+）细胞和SMC对嘌呤的反应表明SMC不太可能是结肠肌肉中嘌呤能神经传递的靶点。
Enteric inhibitory neurotransmission is an important feature of the neural regulation of gastrointestinal motility. Purinergic neurotransmission, via P2Y(1) receptors, mediates one phase of inhibitory neural control. For decades, ATP has been assumed to be the purinergic neurotransmitter and smooth muscle cells (SMCs) have been considered the primary targets for inhibitory neurotransmission. Recent experiments have cast doubt on both of these assumptions and suggested that another cell type, platelet-derived growth factor receptor-alpha-positive (PDGFR alpha(+)) cells, is the target for purinergic neurotransmission. We compared responses of PDGFR alpha(+) cells and SMCs to several purine compounds to determine if these cells responded in a manner consistent with enteric inhibitory neurotransmission. ATP hyperpolarized PDGFR alpha(+) cells but depolarized SMCs. Only part of the ATP response in PDGFR alpha(+) cells was blocked by MRS 2500, a P2Y(1) antagonist. ADP, MRS 2365, beta-NAD, and adenosine 5-diphosphate-ribose, P2Y(1) agonists, hyperpolarized PDGFR alpha(+) cells, and these responses were blocked by MRS 2500. Adenosine 5-diphosphate-ribose was more potent in eliciting hyperpolarization responses than beta-NAD. P2Y(1) agonists failed to elicit responses in SMCs. Small hyperpolarization responses were elicited in SMCs by a small-conductance Ca2+-activated K+ channel agonist, cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, consistent with the low expression and current density of small-conductance Ca2+-activated K+ channels in these cells. Large-amplitude hyperpolarization responses, elicited in PDGFR alpha(+) cells, but not SMCs, by P2Y(1) agonists are consistent with the generation of inhibitory junction potentials in intact muscles in response to purinergic neurotransmission. The responses of PDGFR alpha(+) cells and SMCs to purines suggest that SMCs are unlikely targets for purinergic neurotransmission in colonic muscles.