Department of Physiology and Cell Biology, College of Medicine, Ohio State University, Columbus, OH, USA.
Br J Pharmacol. 2010 Jan;159(1):222-36. doi: 10.1111/j.1476-5381.2009.00516.x. Epub 2009 Nov 27.
Urocortins (Ucns) 1, 2 and 3 are corticotropin-releasing factor (CRF)-related neuropeptides and may be involved in neural regulation of colonic motor functions. Nevertheless, details of the neural mechanism of action for Ucns have been unclear. We have, here, tested the hypothesis that Ucns act in the enteric nervous system (ENS) to influence colonic motor behaviour.
We used intracellular recording with 'sharp' microelectrodes, followed by intraneuronal injection of biocytin, and immunohistochemical localization of CRF(1) and CRF(2) receptors in guinea pig colonic tissue.
Application of Ucn1 depolarized membrane potentials and elevated excitability in 58% of AH-type and 60% of S-type colonic myenteric neurons. In most of the neurons tested, depolarizing responses evoked by Ucn-1 were suppressed by the CRF(1) receptor antagonist NBI 27914, but were unaffected by the CRF(2) receptor antagonist antisauvagine-30. The selective CRF(2) receptor agonists, Ucn2 and Ucn3, evoked depolarizing responses in 12 and 8% of the AH-type myenteric neurons, respectively, and had no effect on S-type neurons. Antisauvagine-30, but not NBI 27914, suppressed these Ucn2- and Ucn3-evoked responses. Immunohistochemical staining identified CRF(1) as the predominant CRF receptor subtype expressed by ganglion cell somas, while CRF(2)-immunoreactive neuronal somas were sparse. Ucns did not affect excitatory synaptic transmission in the ENS.
The results suggest that Ucns act as neuromodulators to influence myenteric neuronal excitability. The excitatory action of Ucn1 in myenteric neurons was primarily at CRF(1) receptors, and the excitatory action of Ucn2 and Ucn3 was at CRF(2) receptors.
尿皮质素（Ucns）1、2 和 3 是促肾上腺皮质激素释放因子（CRF）相关神经肽，可能参与结肠运动功能的神经调节。然而，Ucns 的神经作用机制细节尚不清楚。在这里，我们假设 Ucns 在肠神经系统（ENS）中发挥作用，以影响结肠运动行为。
我们使用带有“尖锐”微电极的细胞内记录，随后进行神经元内注射生物胞素，并在豚鼠结肠组织中进行 CRF(1) 和 CRF(2) 受体的免疫组织化学定位。
Ucn1 的应用使 58%的 AH 型和 60%的 S 型结肠肌间神经元的膜电位去极化并提高兴奋性。在大多数测试的神经元中，Ucn-1 引起的去极化反应被 CRF(1) 受体拮抗剂 NBI 27914 抑制，但不受 CRF(2) 受体拮抗剂 antisauvagine-30 的影响。选择性 CRF(2) 受体激动剂 Ucn2 和 Ucn3 分别使 12%和 8%的 AH 型肌间神经元产生去极化反应，对 S 型神经元没有影响。Antisauvagine-30，但不是 NBI 27914，抑制了这些 Ucn2 和 Ucn3 引起的反应。免疫组织化学染色鉴定 CRF(1) 为表达最多的 CRF 受体亚型，而 CRF(2)-免疫反应性神经元体稀少。Ucns 不影响 ENS 中的兴奋性突触传递。
结果表明，Ucns 作为神经调质发挥作用，影响肌间神经元的兴奋性。Ucn1 在肌间神经元中的兴奋作用主要在 CRF(1) 受体上，而 Ucn2 和 Ucn3 的兴奋作用在 CRF(2) 受体上。
