Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stomach and small intestine receive an efferent innervation from the dorsal motor nucleus of the vagus (DMX). The current experiments were undertaken as a partial test of the hypothesis that the CNS innervates only a small number of command neurons in a restricted number of enteric ganglia. The anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) was injected into the DMX by iontophoresis, and 10-21 days later PHA-L was visualized in the bowel by immunofluorescence. Varicose vagal efferent fibers, labeled by PHA-L, were found in the myenteric plexus as far distally as the ileo-colic junction. PHA-L-labeled varicose axons were rare in comparison to nonlabeled fibers, entered a minority of myenteric ganglia, and contacted a small proportion of the neurons. Ganglia thus innervated by vagal efferent fibers were more numerous in the stomach than in the small intestine. Within the stomach, these ganglia were common in the antrum than in the corpus and none were found in the wall of the rumen. Innervated ganglia in the small intestine became progressively more sparse distally. No PHA-L-labeled axons were observed in the submucosal plexus, thus raising the possibility that vagal modulation of secretomotor responses involves an intermediate synapse in the myenteric plexus. Nonvaricose bundles of PHA-L-labeled fibers were also observed. These bundles appeared to utilize the connectives of the myenteric plexus as a pathway within which to descend within the bowel. Vagal efferent bundles were found to pass through the pyloric sphincter to enter the small intestine from the stomach; thus vagal fibers can reach the distal intestine by an intraenteric route that is not lesioned by crushing mesenteric nerves. The existence of this pathway affects the interpretation of experiments seeking to utilize such lesions to distinguish intrinsic from extrinsic neurites. Possible target neurons of the vagal efferent innervation were identified by simultaneously demonstrating the immunoreactivities of 5-hydroxytryptamine (5-HT), vasoactive intestinal polypeptide (VIP), enkephalin (ENK), galanin (GAL), and tyrosine hydroxylase (TH) along with that of PHA-L. Vagal terminals in the myenteric plexus appeared selectively to contact 5-HT- and, to a significantly lesser extent, VIP-, but not ENK- or GAL-immunoreactive neurons. Apparent vagal innervation of 5-HT-immunoreactive neurons was significantly more common in the duodenum, where a majority of the 5-HT-immunoreactive cells were encircled by varicose PHA-L-labeled axons, than in the stomach.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Identification of vagal efferent fibers and putative target neurons in the enteric nervous system of the rat. 256 99

Small bowel transplantation (SBT) is associated with poorly understood enteric dysfunction. The study of SBT in mice is hindered by the technical difficulty of orthotopic SBT in the mouse. Our aim was to develop an easy preparation of extrinsic denervation of the entire jejunoileum in mice as a model of orthotopic SBT. All neurolymphatic tissues accompanying the superior mesenteric artery (SMA) and vein (SMV) were ligated just distal to the middle colic vessels. The SMA and SMV were then stripped of investing adventitia, and the mesentery to jejunum and colon were transected radially. Jejunum and colon were not transected and reanastomosed. To confirm extrinsic denervation 1, 3, and 6 months later, segments of small bowel were stained for protein gene product 9.5 (PGP9.5) and tyrosine hydroxylase (TH). Tyrosine hydroxylase immunoreactive intensity was then quantified using a semiquantitative analysis. Immunohistochemical fluorescence showed persistence of PGP9.5 immunoreactivity confirming enteric nerves in jejunoileum; however, there was no TH immunoreactivity in jejunoileum in denervated mice despite the expected preservation of TH immunoreactivity in the still-innervated duodenum at 1 month. At 3 months, sparse immunoreactivity for TH was present, and by 6 months, reinnervation of TH-containing nerves appeared similar to controls. Quantification of intensity at each time-point further confirmed this trend. This technique in the mouse accomplishes a complete extrinsic denervation of jejunoileum early postoperatively (1 and 3 months); reinnervation occurs by 6 months. This is an easily learned murine model of orthotopic SBT.
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PMID:Development of a simple model of extrinsic denervation of the small bowel in mouse. 1750 53

Equine ileocolonic aganglionosis, which is also called lethal white foal syndrome (LWFS), is a severe congenital condition characterized by the unsuccessful colonization of neural crest progenitors in the caudal part of the small intestine and the entire large intestine. LWFS, which is attributable to a mutation in the endothelin receptor B gene, is the horse equivalent of Hirschsprung's disease in humans. Affected foals suffer from aganglionosis or hypoganglionosis of the enteric ganglia resulting in intestinal akinesia and colic. In other species with aganglionosis, fibers of extrinsic origin show an abnormal distribution pattern within the gut wall, but we have no information to date regarding this occurrence in horses. Our present aim is to investigate the distribution of extrinsic sympathetic and sensory neural fibers in LWFS, focusing on ileum and the pelvic flexure of the colon of two LWFS foals compared with a control subject. The sympathetic fibers were immunohistochemically identified with the markers tyrosine hydroxylase and dopamine beta-hydroxylase. The extrinsic sensory fibers were identified with the markers Substance P (SP) and calcitonin gene-related peptide (CGRP). Since SP and CGRP are also synthesized by subclasses of horse intramural neurons, LWFS represents a good model for the selective study of extrinsic fiber distribution. Affected foals showed large bundles of extrinsic fibers, compared with the control, as observed in Hirschsprung's disease. Furthermore, altered adrenergic pathways were observed, prominently in the pelvic flexure. The numbers of SP- and CGRP-immunoreactive fibers in the muscle, a target of enteric neurons, were dramatically reduced, whereas fibers deduced to be extrinsic sensory axons persisted around submucosal blood vessels. Fiber numbers in the mucosa were reduced. Thus, extrinsic innervation, contributing to modulate enteric functions, might also be affected during LWFS.
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PMID:Extrinsic innervation of ileum and pelvic flexure of foals with ileocolonic aganglionosis. 2723 Feb 28