Dept. of Medicine, The Johns Hopkins Univ. School of Medicine, Baltimore, MD 21224, USA.
Am J Physiol Gastrointest Liver Physiol. 2011 Mar;300(3):G485-93. doi: 10.1152/ajpgi.00361.2010. Epub 2010 Dec 9.
Clinical studies implicate adenosine acting on esophageal nociceptive pathways in the pathogenesis of noncardiac chest pain originating from the esophagus. However, the effect of adenosine on esophageal afferent nerve subtypes is incompletely understood. We addressed the hypothesis that adenosine selectively activates esophageal nociceptors. Whole cell perforated patch-clamp recordings and single-cell RT-PCR analysis were performed on the primary afferent neurons retrogradely labeled from the esophagus in the guinea pig. Extracellular recordings were made from the isolated innervated esophagus. In patch-clamp studies, adenosine evoked activation (inward current) in a majority of putative nociceptive (capsaicin-sensitive) vagal nodose, vagal jugular, and spinal dorsal root ganglia (DRG) neurons innervating the esophagus. Single-cell RT-PCR analysis indicated that the majority of the putative nociceptive (transient receptor potential V1-positive) neurons innervating the esophagus express the adenosine receptors. The neural crest-derived (spinal DRG and vagal jugular) esophageal nociceptors expressed predominantly the adenosine A(1) receptor while the placodes-derived vagal nodose nociceptors expressed the adenosine A(1) and/or A(2A) receptors. Consistent with the studies in the cell bodies, adenosine evoked activation (overt action potential discharge) in esophageal nociceptive nerve terminals. Furthermore, the neural crest-derived jugular nociceptors were activated by the selective A(1) receptor agonist CCPA, and the placodes-derived nodose nociceptors were activated by CCPA and/or the selective adenosine A(2A) receptor CGS-21680. In contrast to esophageal nociceptors, adenosine failed to stimulate the vagal esophageal low-threshold (tension) mechanosensors. We conclude that adenosine selectively activates esophageal nociceptors. Our data indicate that the esophageal neural crest-derived nociceptors can be activated via the adenosine A(1) receptor while the placodes-derived esophageal nociceptors can be activated via A(1) and/or A(2A) receptors. Direct activation of esophageal nociceptors via adenosine receptors may contribute to the symptoms in esophageal diseases.
临床研究表明，腺苷通过作用于食管伤害性感受器通路在非心源性胸痛的发病机制中起作用，这种胸痛源自食管。然而，腺苷对食管传入神经亚型的影响尚不完全清楚。我们提出假设，即腺苷选择性地激活食管伤害感受器。我们对豚鼠食管逆行标记的初级传入神经元进行了全细胞膜片钳记录和单细胞 RT-PCR 分析，并对分离的感觉神经支配的食管进行了细胞外记录。在膜片钳研究中，腺苷诱发了大多数假定的伤害性（辣椒素敏感）迷走神经结状、迷走颈和脊髓背根神经节（DRG）神经元的激活（内向电流），这些神经元支配食管。单细胞 RT-PCR 分析表明，支配食管的大多数假定伤害感受器（瞬时受体电位 V1 阳性）神经元表达腺苷受体。神经嵴衍生的（脊髓 DRG 和迷走颈）食管伤害感受器主要表达腺苷 A(1)受体，而神经嵴衍生的迷走结状伤害感受器表达腺苷 A(1)和/或 A(2A)受体。与细胞体研究一致，腺苷诱发了食管伤害性神经末梢的激活（明显动作电位放电）。此外，选择性 A(1)受体激动剂 CCPA 激活了神经嵴衍生的颈静脉伤害感受器，而神经嵴衍生的结状伤害感受器被 CCPA 和/或选择性腺苷 A(2A)受体 CGS-21680 激活。与食管伤害感受器相反，腺苷未能刺激迷走食管低阈值（张力）机械感受器。我们得出结论，腺苷选择性地激活食管伤害感受器。我们的数据表明，食管神经嵴衍生的伤害感受器可以通过腺苷 A(1)受体激活，而神经嵴衍生的食管伤害感受器可以通过 A(1)和/或 A(2A)受体激活。通过腺苷受体直接激活食管伤害感受器可能导致食管疾病的症状。
