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K R Jessen

Publications and source records attributed to K R Jessen.

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GABA and the enteric nervous system. A neurotransmitter function?

GABA and GABA-related properties in the enteric nervous system of the gastrointestinal tract, the third and most complex division of the vertebrate autonomic nervous system, have been the subject of relatively few studies. This chapter aims at being a comprehensive review of these investigations. With respect to GABA the enteric nervous system shows in some respects similarities with, and in others, notable differences from other parts of the peripheral nervous system. Like the cell bodies of other autonomic and sensory neurons, the cell bodies of enteric neurons possess bicuculline and picrotoxin sensitive GABA receptors, the activation of which leads to depolarization, probably mediated by increase in Cl- conductance. Further, in common with other peripheral glia, the cell membrane of the enteric glial cells appears to contain beta-alanine sensitive high affinity transport sites by which they can accumulate exogenous GABA. However, the present evidence, although not completely conclusive, suggests that unlike other parts of the peripheral nervous system, the enteric ganglia may contain a population of GABA-ergic neurons; in vertebrates such neurons have hitherto been thought to be present in the brain and spinal cord only. At present the mst important single strand of evidence for this notion is the demonstration of a population of enteric neurons possessing high affinity transport sites for GABA, while it is supported by studies of GAD and GABA content, the effects of GABA receptors blockade on gut motility and GABA release.

Animals↗

Glial cells in the enteric nervous system contain glial fibrillary acidic protein.

The complex nervous networks found throughout the mammalian gut--the enteric nervous system--are histologically, ultrastructurally, and, to some extent, functionally--similar to the central nervous system. The glial cells of the small enteric ganglia are generally classified as Schwann or satellite cells, since they are found in the peripheral nervous system, possess nuclei which ultrastructurally resemble those of Schwann cells and are derived from the neural crest. However, it has been argued that these cells resemble astrocytes of the central nervous system with respect to gross and fine structure, and their relationship with the enteric neurones and their processes. In immunohistochemical studies of these cells, both in frozen sections of gut wall and in tissue culture preparations of the enteric plexuses, we found evidence that the enteric glial cells are rich in glial fibrillary acidic protein (GFAP), a protein associated with the 100 A glial intermediate filaments, and hitherto believed to be specific to astrocytes of the central nervous system only.

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Peptide-containing neurones connect the two ganglionated plexuses of the enteric nervous system.

The enteric nervous system (ENS) of the mammalian gut consists principally of two ganglionated plexuses, the myenteric and submucous, which are embedded in the gut wall. Little is known about the anatomical and functional connections between the two plexuses and further clarification of their relationship is of central importance for the understanding of the ENS. In the present study we have approached this problem in a new way, using methods we have previously developed for maintaining the myenteric and submucous plexuses separately in vitro for several weeks. In an immunohistochemical study of these preparations and also of sections from normal and extrinsically denervated gut wall, we have found evidence for reciprocal projections between the myenteric and submucous plexuses, by nerve fibres containing two putative neurotransmitters, vasoactive intestinal polypeptide (VIP) and substance P (ref. 5) (see Fig. 1). Our observations were supported by radioimmunoassay of tissue extracts. These results suggest that one of the roles of these peptides in the gut is to coordinate the function of the two enteric plexuses.

Animals↗

GABA may be a neurotransmitter in the vertebrate peripheral nervous system.

gamma-Aminobutyric acid (GABA) is an inhibitory neurotransmitter in the peripheral nervous system of certain invertebrates and is thought to be a major transmitter in the vertebrate central nervous system. In this report we present evidence that GABA may also be a neurotransmitter in the vertebrate peripheral autonomic nervous system. We have used light and electron microscopic autoradiography to analyse high-affinity uptake of 3H-GABA into the myenteric plexus of the guinea pig taenia coli, both in situ and in a tissue culture preparation. In the isolated myenteric plexus, we have measured the specific activity of glutamic acid decarboxylase (GAD; EC 4.1.1.15), the enzyme responsible for conversion of glutamic acid to GABA in GABAergic neurones, and assessed the ability of this tissue to accumulate 3H-GABA newly synthesised from 3H-glutamic acid. Furthermore, we have measured the levels of endogenous GABA in strips of taenia coli containing the myenteric plexus.

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Intracellular localization of acetylcholinesterase in nerve terminals and capillaries of the rat superior cervical ganglion.

The ultrastructural localization of acetylcholinesterase (AChE) has been studied in the superior cervical ganglion of the rat. Previous descriptions of the general pattern of localization were confirmed, but in addition, AChE reaction product was found within vesicles in preganglionic nerve terminals, and in pinocytotic vesicles and along the basement lamina of capillaries. There was indication of a continuity between AChE reaction product in the cisternae of the rough endoplasmic reticulum of the principal ganglion cells and extracellular reaction product. These observations are discussed with particular reference to AChE as a secretory protein.

Acetylcholinesterase↗

A cell surface protein of astrocytes, Ran-2, distinguishes non-myelin-forming Schwann cells from myelin-forming Schwann cells.

Defining the molecular phenotype of adult glial cells in the peripheral nervous system in situ forms a good basis for subsequent studies on the development of these cells, and for determining the role of neurons in the attainment and maintenance of the mature glial phenotype. We report here the characterization of the glial surface antigen, Ran-2, and describe its distribution in the peripheral and central nervous system of adult rats. Immunoprecipitation of the antigen from cultured astrocytes with monoclonal Ran-2, antibodies, showed that Ran-2 is a protein with an apparent molecular weight of 140,000 daltons. In immunofluorescence studies of teased nerve preparations, Ran-2 was found on the surface of non-myelin-forming Schwann cells in all nerves surveyed, i.e. the sciatic, dorsal and ventral roots, cervical sympathetic trunk and the brachial plexus. In contrast, it was not detected immunohistochemically on myelin-forming Schwann cells. The antigen was also absent, or present at very low levels, on the satellite cells of dorsal root sensory ganglia, although, as we reported previously, it was present on the glial cells of the enteric nervous system. The Ran-2 antigen was also associated with perineurial cells. In short-term cell cultures of the sciatic nerve and cervical sympathetic trunk from 19-day-old rats, Ran-2 could be localized on the surface of individual viable Schwann cells. In the central nervous system, the antigen was present on astrocytes in sections of the optic nerve.

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