Krantis A, Nichols K, Staines W
Department of Cellular and Molecular Medicine, University of Ottawa, Ont., Canada.
J Auton Nerv Syst. 1998 Jan 19;68(1-2):33-42. doi: 10.1016/s0165-1838(97)00113-6.
GABA, somatostatin and enkephalin are neurotransmitters of enteric interneurons and comprise part of the intrinsic neural circuits regulating peristalsis. Within the relaxation phase of reflex peristalsis, nitric oxide (NO) is released by inhibitory motor neurons and perhaps enteric interneurons as well. Previously, we identified by GABA transaminase (GABA-T) immunohistochemistry, a subpopulation of GABAergic interneurons in the human colon which also contain NO synthase activity and hence produce NO. In this study, we have examined further the capacity for cotransmission within the GABAergic innervation in human colon. The expression of two important neuropeptides within GABAergic neurons was determined by combined double-labelled immunocytochemistry using antibodies for GABA-T, enkephalin and somatostatin, together with the demonstration of NO synthase-related NADPH diaphorase staining in cryosectioned colon. Both neuropeptides were found in GABAergic neurons of the colon. The evidence presented herein confirms the colocalization of NO synthase activity and GABA-T immunoreactivity in subpopulations of enteric neurons and further allows the neurochemical classification of GABAergic neurons of the human colon into three subsets: (i) neurons colocalizing somatostatin-like immunoreactivity representing about 40% of the GABAergic neurons, (ii) neurons colocalizing enkephalin-like immunoreactivity, about 9% of the GABAergic neurons and (iii) neurons colocalizing NO synthase activity, about 23% of the GABAergic neurons. This division of GABAergic interneurons into distinct subpopulations of neuropeptide or NO synthase containing cells is consistent with and provides an anatomical correlate for the pharmacology of these transmitters and the pattern of transmitter release during reflex peristalsis.
γ-氨基丁酸（GABA）、生长抑素和脑啡肽是肠内中间神经元的神经递质，构成调节蠕动的内在神经回路的一部分。在反射性蠕动的松弛阶段，一氧化氮（NO）由抑制性运动神经元释放，肠内中间神经元可能也会释放。此前，我们通过GABA转氨酶（GABA-T）免疫组织化学方法，在人类结肠中鉴定出了一群GABA能中间神经元，它们还具有NO合酶活性，因此能产生NO。在本研究中，我们进一步研究了人类结肠中GABA能神经支配内的共传递能力。使用针对GABA-T、脑啡肽和生长抑素的抗体，通过联合双标免疫细胞化学方法，测定了GABA能神经元内两种重要神经肽的表达，并在结肠冰冻切片中显示了与NO合酶相关的NADPH黄递酶染色。在结肠的GABA能神经元中发现了这两种神经肽。本文提供的证据证实了肠神经元亚群中NO合酶活性与GABA-T免疫反应性的共定位，并进一步将人类结肠的GABA能神经元按神经化学分类为三个亚群：（i）共定位生长抑素样免疫反应性的神经元，约占GABA能神经元的40%；（ii）共定位脑啡肽样免疫反应性的神经元，约占GABA能神经元的9%；（iii）共定位NO合酶活性的神经元，约占GABA能神经元的23%。将GABA能中间神经元分为含神经肽或NO合酶的不同亚群，这与这些递质的药理学以及反射性蠕动期间递质释放模式一致，并提供了解剖学上的关联。
