Classical concepts of peripheral neurotransmission were insufficient to explain enteric inhibitory neurotransmission. Geoffrey Burnstock and colleagues developed the idea that ATP or a related purine satisfies the criteria for a neurotransmitter and serves as an enteric inhibitory neurotransmitter in GI muscles. Cloning of purinergic receptors and development of specific drugs and transgenic mice have shown that enteric inhibitory responses depend upon P2Y₁ receptors in post-junctional cells. The post-junctional cells that transduce purinergic neurotransmitters in the GI tract are PDGFRα⁺ cells and not smooth muscle cells (SMCs). PDGFRα⁺ cells express P2Y₁ receptors, are activated by enteric inhibitory nerve stimulation and generate Ca²⁺ oscillations, express small-conductance Ca²⁺-activated K⁺ channels (SK3), and generate outward currents when exposed to P2Y₁ agonists. These properties are consistent with post-junctional purinergic responses, and similar responses and effectors are not functional in SMCs. Refinements in methodologies to measure purines in tissue superfusates, such as high-performance liquid chromatography (HPLC) coupled with etheno-derivatization of purines and fluorescence detection, revealed that multiple purines are released during stimulation of intrinsic nerves. β-NAD⁺ and other purines, better satisfy criteria for the purinergic neurotransmitter than ATP. HPLC has also allowed better detection of purine metabolites, and coupled with isolation of specific types of post-junctional cells, has provided new concepts about deactivation of purine neurotransmitters. In spite of steady progress, many unknowns about purinergic neurotransmission remain and require additional investigation to understand this important regulatory mechanism in GI motility.

周围神经传递的经典概念不足以解释肠道抑制性神经传递。Geoffrey Burnstock 及其同事提出了这样一种观点，即 ATP 或相关的嘌呤满足神经递质的标准，并在 GI 肌肉中充当肠抑制性神经递质。嘌呤受体的克隆以及特定药物和转基因小鼠的开发表明，肠道抑制反应依赖于连接后细胞中的P2Y _1受体。在胃肠道中转导嘌呤能神经递质的连接后细胞是 PDGFRα ⁺细胞，而不是平滑肌细胞 (SMC)。PDGFRα ⁺细胞表达 P2Y ₁受体被肠抑制性神经刺激激活并产生Ca ²⁺振荡，表达小电导Ca ²⁺激活的K ⁺通道(SK3)，并在暴露于P2Y ₁激动剂时产生外向电流。这些特性与连接后嘌呤能反应一致，并且类似的反应和效应器在 SMC 中不起作用。测量组织灌流液中嘌呤的方法的改进，如高效液相色谱法 (HPLC) 以及嘌呤的乙烯衍生化和荧光检测，表明在刺激内在神经期间会释放多种嘌呤。β-NAD ⁺和其他嘌呤，比 ATP 更能满足嘌呤能神经递质的标准。HPLC 还可以更好地检测嘌呤代谢物，并结合特定类型的连接后细胞的分离，提供了关于嘌呤神经递质失活的新概念。尽管取得了稳步进展，但关于嘌呤能神经传递的许多未知数仍然存在，需要进一步研究以了解胃肠道运动的这一重要调节机制。