Department of Surgery, Hospital de Mataró, Barcelona, Spain.
Neurogastroenterol Motil. 2011 Jan;23(1):e11-25. doi: 10.1111/j.1365-2982.2010.01602.x. Epub 2010 Oct 3.
The neurotransmitters mediating inhibitory pathways to internal anal sphincter (IAS) have not been fully characterized. Our aim was to assess the putative release of nitric oxide, purines and vasoactive intestinal peptide (VIP) from inhibitory motor neurons (MNs) and their role in the myogenic tone, resting membrane potential (RMP) of smooth muscle cells (SMC), spontaneous inhibitory junction potentials (sIJP), mechanical relaxation, and IJP induced by electrical field stimulation (EFS) or nicotine.
Rat IAS strips were studied using organ baths, microelectrodes, and immunohistochemistry.
Internal anal sphincter strips developed active myogenic tone (0.31 g), enhanced and stabilized by prostaglandin F(2α) (PGF2α). L-NNA (1 mmol L(-1)) depolarized SMC and increased tone but did not modify sIJP. In contrast, the specific P2Y(1) receptor antagonist MRS2500 (1 μmol L(-1)) did not modify the RMP or the basal tone but abolished sIJP. Electrical field stimulation and nicotine (10 μmol L(-1)) caused IAS relaxation (-45.9%VS-52.2%), partially antagonized by L-NNA (35%-45%, P ≤ 0.05) and fully abolished by MRS2500 (P ≤ 0.001). Electrical field stimulation induced a biphasic inhibitory junction potential (IJP), the initial fast component was selectively blocked by MRS2500 and the sustained slow component was blocked by L-NNA. Vasoactive intestinal peptide 6-28 (0.1 μmol L(-1)) or α-chymotrypsin (10 U mL(-1)) did not modify the RMP, sIJP, EFS-induced IJP, or relaxation. P2Y(1) receptors were immunolocalized in the circular SMC of IAS.
CONCLUSIONS & INFERENCES: The effects of inhibitory MNs on rat IAS are mediated by a functional co-transmission process involving nitrergic and purinergic pathways through P2Y(1) receptors with specific and complementary roles on the control of tone, sIJP, and hyperpolarization and relaxation of IAS following stimulation of inhibitory MNs.
介导内肛门括约肌（IAS）抑制途径的神经递质尚未完全确定。我们的目的是评估假定从抑制运动神经元（MNs）释放一氧化氮、嘌呤和血管活性肠肽（VIP），以及它们在平滑肌细胞（SMC）的肌源性张力、静息膜电位（RMP）、自发性抑制性突触后电位（sIJP）、机械松弛以及电场刺激（EFS）或尼古丁诱导的 IJP 中的作用。
使用器官浴、微电极和免疫组织化学方法研究大鼠 IAS 带。
内肛门括约肌带表现出主动肌源性张力（0.31g），由前列腺素 F2α（PGF2α）增强和稳定。L-NNA（1mmol/L）使 SMC 去极化并增加张力，但不改变 sIJP。相反，特异性 P2Y1 受体拮抗剂 MRS2500（1μmol/L）不改变 RMP 或基础张力，但消除了 sIJP。EFS 和尼古丁（10μmol/L）引起 IAS 松弛（-45.9%VS-52.2%），L-NNA 部分拮抗（35%-45%，P≤0.05），MRS2500 完全拮抗（P≤0.001）。EFS 诱导双相抑制性突触后电位（IJP），初始快速成分被 MRS2500 选择性阻断，持续缓慢成分被 L-NNA 阻断。血管活性肠肽 6-28（0.1μmol/L）或糜蛋白酶（10U/mL）不改变 RMP、sIJP、EFS 诱导的 IJP 或松弛。P2Y1 受体在 IAS 的环形 SMC 中免疫定位。
抑制性 MN 对大鼠 IAS 的影响是通过涉及 P2Y1 受体的功能性共传递过程介导的，该过程在控制 IAS 张力、sIJP 以及刺激抑制性 MN 后 IAS 的超极化和松弛方面具有特定和互补的作用。
