Battish R, Cao G Y, Lynn R B, Chakder S, Rattan S
Department of Medicine, Division of Gastroenterology and Hepatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Am J Physiol Gastrointest Liver Physiol. 2000 Jan;278(1):G148-55. doi: 10.1152/ajpgi.2000.278.1.G148.
Recent investigations have suggested carbon monoxide (CO) as a putative messenger molecule. Although several studies have implicated the heme oxygenase (HO) pathway, responsible for the endogenous production of CO, in the neuromodulatory control of the internal anal sphincter (IAS), its exact role is not known. Nitric oxide, produced by neuronal nitric oxide synthase (nNOS) of myenteric neurons, is an important inhibitory neural messenger molecule mediating nonadrenergic noncholinergic (NANC) relaxation of the IAS. The present studies were undertaken to investigate in detail the presence and coexistence of heme oxygenase-2 (HO-2) with nNOS in the opossum anorectum. In perfusion-fixed, frozen-sectioned tissue, HO-2 immunoreactive (IR) and nNOS IR nerves were identified using immunocytochemistry. Ganglia containing HO-2 IR neuronal cell bodies were present in the myenteric and submucosal plexuses throughout the entire anorectum. Colocalization of HO-2 IR and nNOS IR was nearly 100% in the IAS and decreased proximally from the anal verge. In the rectum, colocalization of HO-2 IR and nNOS IR was approximately 70%. Additional confocal microscopy studies using c-Kit staining demonstrated the localization of HO-2 IR and nNOS IR in interstitial cells of Cajal (ICC) of the anorectum. From the high rate of colocalization of HO-2 IR and nNOS IR in the IAS as well as the localization of HO-2 IR and nNOS IR in ICC in conjunction with earlier studies of the HO pathway, we speculate an interaction between HO and NOS pathways in the NANC inhibitory neurotransmission of the IAS and rectum.
最近的研究表明一氧化碳（CO）是一种假定的信使分子。尽管有几项研究表明负责内源性产生CO的血红素加氧酶（HO）途径参与了肛门内括约肌（IAS）的神经调节控制，但其确切作用尚不清楚。由肌间神经丛神经元型一氧化氮合酶（nNOS）产生的一氧化氮是介导IAS非肾上腺素能非胆碱能（NANC）舒张的重要抑制性神经信使分子。本研究旨在详细调查负鼠肛门直肠中血红素加氧酶-2（HO-2）与nNOS的存在及共存情况。在灌注固定、冰冻切片的组织中，采用免疫细胞化学方法鉴定HO-2免疫反应性（IR）神经和nNOS IR神经。在整个肛门直肠的肌间神经丛和黏膜下神经丛中均存在含有HO-2 IR神经元细胞体的神经节。HO-2 IR与nNOS IR在IAS中的共定位率接近100%，并从肛缘向近端降低。在直肠中，HO-2 IR与nNOS IR的共定位率约为70%。使用c-Kit染色的额外共聚焦显微镜研究显示了HO-2 IR和nNOS IR在肛门直肠Cajal间质细胞（ICC）中的定位。基于HO-2 IR与nNOS IR在IAS中的高共定位率以及HO-2 IR和nNOS IR在ICC中的定位，结合早期对HO途径的研究，我们推测HO与NOS途径在IAS和直肠的NANC抑制性神经传递中存在相互作用。
