Department of Cell Biology, Physiology and Immunology and Neuroscience Institute, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Neurogastroenterol Motil. 2013 Mar;25(3):e170-82. doi: 10.1111/nmo.12060. Epub 2013 Jan 17.
Pharmacological studies using selective P2Y(1) antagonists, such as MRS2500, and studies with P2Y(1)(-/-) knockout mice have demonstrated that purinergic neuromuscular transmission is mediated by P2Y(1) receptors in the colon. The aim of the present study was to test whether P2Y(1) receptors are involved in purinergic neurotransmission in the antrum and cecum.
Microelectrode recordings were performed on strips from the antrum and cecum of wild type animals (WT) and P2Y(1)(-/-) mice.
In the antrum, no differences in resting membrane potential and slow wave activity were observed between groups. In WT animals, electrical field stimulation elicited a MRS2500-sensitive inhibitory junction potential (IJP). In P2Y(1)(-/-) mice, a nitrergic IJP (N(ω) -nitro-l-arginine-sensitive), but not a purinergic IJP was recorded. This IJP was equivalent to the response obtained in strips from WT animals previously incubated with MRS2500. Similar results were obtained in the cecum: 1- the purinergic IJP (MRS2500-sensitive) recorded in WT animals was absent in P2Y(1)(-/-) mice 2- nitrergic neurotransmission was preserved in both groups. Moreover, 1- spontaneous IJP (MRS2500-sensitive) could be recorded in WT, but not in P2Y(1)(-/-) mice 2- MRS2365 a P2Y(1) agonist caused smooth muscle hyperpolarization in WT, but not in P2Y(1) (-/-) animals, and 3- β-NAD caused smooth muscle hyperpolarization both in WT and P2Y(1)(-/-) animals.
CONCLUSIONS & INFERENCES: 1- P2Y(1) receptor is the general mechanism of purinergic inhibition in the gastrointestinal tract, 2- P2Y(1)(-/-) mouse is a useful animal model to study selective impairment of purinergic neurotransmission and 3- P2Y(1)(-/-) mouse might help in the identification of purinergic neurotransmitter(s).
使用选择性 P2Y(1) 拮抗剂（如 MRS2500）的药理学研究和 P2Y(1)(-/-) 基因敲除小鼠的研究表明，嘌呤能神经肌肉传递是由结肠中的 P2Y(1) 受体介导的。本研究的目的是测试 P2Y(1) 受体是否参与胃窦和盲肠中的嘌呤能神经传递。
在野生型动物（WT）和 P2Y(1)(-/-) 小鼠的胃窦和盲肠条上进行微电极记录。
在胃窦中，各组之间的静息膜电位和慢波活动没有差异。在 WT 动物中，电刺激引发 MRS2500 敏感的抑制性突触后电位（IJP）。在 P2Y(1)(-/-) 小鼠中，记录到一种非肾上腺素能 IJP（N(ω)-硝基-l-精氨酸敏感），而不是嘌呤能 IJP。这种 IJP 与先前用 MRS2500 孵育的 WT 动物条带中获得的反应相当。在盲肠中也得到了类似的结果：1-P2Y(1)(-/-) 小鼠中记录到的嘌呤能 IJP（MRS2500 敏感）在 WT 动物中缺失；2-两组的非肾上腺素能神经传递均得以保留。此外，1-WT 中可记录到自发性 IJP（MRS2500 敏感），而 P2Y(1)(-/-) 小鼠中则不能；2-MRS2365 是一种 P2Y(1) 激动剂，可使 WT 动物的平滑肌超极化，但不能使 P2Y(1)(-/-) 动物的平滑肌超极化；3-β-NAD 可使 WT 和 P2Y(1)(-/-) 动物的平滑肌超极化。
1-P2Y(1) 受体是胃肠道嘌呤能抑制的一般机制；2-P2Y(1)(-/-) 小鼠是研究选择性嘌呤能神经传递损伤的有用动物模型；3-P2Y(1)(-/-) 小鼠可能有助于鉴定嘌呤能神经递质。
