De Giorgio R, Zittel T T, Parodi J E, Becker J M, Brunicardi F C, Go V L, Brecha N C, Sternini C
CURE: VA/UCLA Gastroenteric Biology Center VAMC-Wadsworth 90073, USA.
J Auton Nerv Syst. 1995 Jan 20;51(1):37-47. doi: 10.1016/0165-1838(95)80005-u.
The mammalian gallbladder is innervated by a well-developed intrinsic neural network. However, little is known about the neurochemistry and organization of the innervation of this organ in humans. The aim of this study was to analyze the distribution of immunoreactivity (IR) for the neuropeptides, vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), tachykinins (TK) and calcitonin gene-related peptide (CGRP) in the human gallbladder by means of immunohistochemistry. Neuropeptide-IRs are found in neurons and processes of the two ganglionated plexuses, i.e., the innermost plexus located in the lamina propria at the base of the mucosal folds, and the outermost plexus situated within the fibro-muscular layer. In these two plexuses, VIP-, NPY- and TK-IRs are present in ganglion cells and varicose fibers, whereas CGRP-IR is confined to nerve processes. VIP-IR is present in most, if not all, neurons. NPY- and TK-IRs are also found in many neurons. The densities of the peptide-IR nerves in the mucosa are NPY and VIP > TK >> CGRP, and in the fibro-muscular layer are NPY > VIP and TK > CGRP. The vasculature is richly innervated by NPY-IR nerves, which are mostly perivascular. CGRP-, VIP- and TK-IR processes are found only occasionally around blood vessels and in a paravascular position. Double-label studies demonstrated that a large number of VIP-containing neurons expresses NPY- or TK-IR. On the other hand, all neurons positive for either NPY- or TK-IR are immunostained for VIP. In agreement with these findings, most of the NPY-IR fibers in the lamina propria and fibro-muscular layer contain VIP-IR, and numerous TK-IR fibers are positive for VIP. However, the perivascular NPY-IR processes do not contain VIP-IR, suggesting an extrinsic origin. In addition, a population of TK-IR processes contains CGRP-IR and presumably originates from extrinsic sources, since CGRP/TK-IR intrinsic neurons could not be detected in the gallbladder. Peptide-IRs have a similar distribution in the neck, body and fundus of the gallbladder. No peptide-containing endocrine/paracrine cells are observed in the epithelium. The presence of peptide-IRs in the ganglionated plexuses and the abundance of peptidergic innervation suggest that peptides exert their effects on gallbladder function by acting directly on tissue targets and influencing intrinsic ganglion cells. Furthermore, the co-localization of more than one peptide in the same neuron raises the possibility that peptides are co-released upon stimulation and might interact at the same target.
哺乳动物的胆囊由一个发育良好的内在神经网络支配。然而，关于人类该器官神经化学和神经支配组织的了解却很少。本研究的目的是通过免疫组织化学分析神经肽、血管活性肠肽（VIP）、神经肽Y（NPY）、速激肽（TK）和降钙素基因相关肽（CGRP）在人胆囊中的免疫反应性（IR）分布。在两个有神经节的神经丛的神经元和突起中发现了神经肽IR，即位于黏膜皱襞底部固有层的最内层神经丛和位于纤维肌层内的最外层神经丛。在这两个神经丛中，VIP-、NPY-和TK-IR存在于神经节细胞和曲张纤维中，而CGRP-IR仅限于神经突起。VIP-IR存在于大多数（如果不是全部）神经元中。NPY-和TK-IR也存在于许多神经元中。黏膜中肽IR神经的密度为NPY和VIP＞TK＞＞CGRP，纤维肌层中为NPY＞VIP且TK＞CGRP。血管系统由NPY-IR神经丰富地支配，这些神经大多位于血管周围。CGRP-、VIP-和TK-IR突起仅偶尔在血管周围和血管旁位置被发现。双重标记研究表明，大量含VIP的神经元表达NPY-或TK-IR。另一方面，所有对NPY-或TK-IR呈阳性的神经元均被VIP免疫染色。与这些发现一致，固有层和纤维肌层中的大多数NPY-IR纤维含有VIP-IR，许多TK-IR纤维对VIP呈阳性。然而，血管周围的NPY-IR突起不含VIP-IR，提示其起源于外部。此外，一群TK-IR突起含有CGRP-IR，推测起源于外部，因为在胆囊中未检测到CGRP/TK-IR固有神经元。肽IR在胆囊颈部、体部和底部有相似的分布。上皮中未观察到含肽的内分泌/旁分泌细胞。有神经节的神经丛中肽IR的存在以及肽能神经支配的丰富表明，肽通过直接作用于组织靶点并影响固有神经节细胞来发挥对胆囊功能的作用。此外，同一神经元中一种以上肽的共定位增加了肽在刺激时共同释放并可能在同一靶点相互作用的可能性。
