Sand Elin, Themner-Persson Anna, Ekblad Eva
Department of Experimental Medical Science, Lund University, Lund, Sweden.
Regul Pept. 2011 Jan 17;166(1-3):68-75. doi: 10.1016/j.regpep.2010.08.011. Epub 2010 Aug 27.
Aims of the present study were to describe the distribution of corticotropin releasing factor (CRF) immunoreactivity in rat small and large intestines, to quantify the percentage of CRF-immunoreactive (CRF-IR) enteric neurons, to reveal possible CRF immunoreactivity in cultured myenteric neurons from rat ileum and to examine if additions of CRF, urocortin 1 (Ucn1), CRF antagonist or vasoactive intestinal peptide (VIP) affect neuronal survival in vitro. Co-localization of CRF- and VIP-immunoreactivity was examined, as well as a possible interplay between CRF and VIP in neuroprotection. Further we wanted to elucidate if mast cells affect neuronal survival via CRF signaling. Networks of CRF-containing nerve cell bodies and fibers were detected in rat intestine. CRF-IR neurons contained to a high degree also VIP. A low number of cultured myenteric neurons was CRF-IR. CRF, Ucn1 or CRF-antagonist did not promote neuronal survival of cultured myenteric neurons, while VIP significantly enhanced neuronal survival. Simultaneous presence of CRF attenuated the VIP mediated increase in neuronal survival. Co-culturing neurons and mast cells resulted in a marked reduction in neuronal survival, not executed via CRF signaling pathways.
CRF is present in enteric neurons and counteracts the neuroprotective effect of VIP in vitro.
本研究的目的是描述促肾上腺皮质激素释放因子（CRF）免疫反应性在大鼠小肠和大肠中的分布，量化CRF免疫反应性（CRF-IR）肠神经元的百分比，揭示大鼠回肠培养的肌间神经元中可能的CRF免疫反应性，并检查添加CRF、尿皮质素1（Ucn1）、CRF拮抗剂或血管活性肠肽（VIP）是否会影响体外神经元存活。研究了CRF和VIP免疫反应性的共定位，以及CRF和VIP在神经保护中的可能相互作用。此外，我们想阐明肥大细胞是否通过CRF信号传导影响神经元存活。在大鼠肠道中检测到含CRF的神经细胞体和纤维网络。CRF-IR神经元也高度含有VIP。少量培养的肌间神经元是CRF-IR。CRF、Ucn1或CRF拮抗剂未促进培养的肌间神经元的神经元存活，而VIP显著提高了神经元存活。CRF的同时存在减弱了VIP介导的神经元存活增加。神经元与肥大细胞共培养导致神经元存活显著降低，这不是通过CRF信号通路实现的。
CRF存在于肠神经元中，并在体外抵消VIP的神经保护作用。
