Comparative study of the release of glutamate and GABA, newly synthesized from glutamine, in various regions of the central nervous system.
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Biomedical subjects
Publications and source records attributed to J C Reubi.
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The role of asparagine as precursor for the neurotransmitter aspartate was investigated in rat striatum in vitro. 14C-asparagine incubated with striatal slices is converted to a great extent to 14C-aspartate which is released in a calcium-dependent manner by high KCl. Furthermore, a frontoparietal cortex ablation of two weeks produces a decrease of more than 70% in the striatal release of newly synthetized 14C-aspartate, whereas the striatal GABA release is unaffected. This suggests that asparagine is a possible precursor in vitro for transmitter aspartate in the striatum. This reaction is dependent on intact corticostriatal fibres.
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Possible morphological correlates of dendritic release sites for dopamine have been investigated in the rat substantia nigra. Electronmicroscopic and freeze etching studies show that nigral dendrites fail to form dendrodendritic contacts but on the contrary are always separated by glial elements, which in turn are connected by multiple gap junctions. No dendro-axonic synapses are present but large specialized symmetrical junctions could provide a possible morphological specialization for a dopamine transfer from presynaptic dendrites to axon endings.
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The organisation of the central nervous system (CNS) is considered from the point of view of the chemical specificity of neurons with respect to their neurotransmitters. The mechanisms of neurotransmission are summarized as well as the approaches used to determine the neurotransmitters of specific CNS pathways. As an example, the neurotransmitters of the basal ganglion and their interactions are presented and their implications for the pathophysiology of Huntington disease and possibly schizophrenia are discussed.
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The effects of GABA, substance P and dopamine on the release of newly synthesized 3H-5-HT were investigated, using slices of rat substantia nigra superfused with L-3H-tryptophan in vitro. GABA (50 micron) had no inhibitory effect on the potassium-evoked-release of 3H-5-HT. Substance P (50 micron) and eledoisin (50 micron) stimulated the spontaneous release of 3H-5-HT. This effect seems to be indirect and is possibly mediated by dopaminergic neurones, since the dopamine antagonist drug alpha-flupenthixol (1 micron) abolished the substance P-evoked release of 5-HT. Furthermore, it was found that substance P (10 micron) stimulated 3H-dopamine release from nigral slices in vitro and the dopaminergic agonist apomorphine (50 micron) also stimulated 3H-5-HT release. Substance P may, therefore, activate nigral dopaminergic neurones which then release dopamine from their dendrites. The release of dopamine may in turn stimulate 5-HT release from terminals of the raphe-nigral pathway.
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A 6 1/2-month-old boy suffering from nonketotic hyperglycinemia has been treated for at least 12 months with oral strychnine. The drug caused improvement of muscle tone, motoricity, vigilance and social behavior. Glycine is one of the putative neurotransmitters of postsynaptic inhibition, particularly at the spinal and reticular levels, strychnine its antagonist at the postsynaptic membrane. Strychnine improved the patient's motoricity presumably by blocking the excessive glycine-mediated inhibition of motoneurons. The beneficial effect of strychnine on vigilance and social behavior is more difficult to explain but may have been related to its antagonism of glycine inhibition of brainstem reticular neurons.
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A pathway having an affinity for glycine has been investigated in the pigeon optic lobe; it originates in the nucleus isthmi pars parvocellularis (Ipc) and terminates in the tectum, In an attempt to obtain evidence that glycine plays a role as a transmitter in this system, the effect of electrical stimulation on release of labeled substances previously injected in the tectum was tested. By perfusing the upper strata of the optic tectum with a push-pull cannula the release of radioactive glycine was shown to be markedly increased by electrical stimulation of Ipc, but not by stimulation of other sites. Ipc stimulation did not affect the efflux of exogenous leucine or urea, whereas a GABA release was observed. With K+ (40 mM) stimulation all amino acids tested were released. It is suggested that the Ipc neuron terminals in the tectum take up glycine and release it upon stimulation of the Ipc nucleus.
The results of visualization of the islet cell tumors of 25 patients after intravenous administration of two isotope-labeled somatostatin analogs (123I-Tyr3-octreotide and 111In-octreotide) are described. The primary tumors, as well as previously often unrecognized distant metastases were visualized in 20 of the 25 patients (80%). Parallel in vitro detection of somatostatin receptors on those tumors that had also been visualized in vivo indicates that the ligand binding to the tumor in vivo indeed represents binding to specific somatostatin receptors. The detection of somatostatin receptors on these tumors in vivo predicted a good suppressive effect of octreotide on hormonal hypersecretion by these tumors. It is an easy, quick, harmless procedure that is valuable for localization of primary endocrine pancreatic tumors and their often radiologically and clinically not yet recognized metastases.
Primary endocrine neoplasms of the biliary tract are exceedingly rare. We report on a 60-year-old man with diarrhea, vomiting and gastroesophageal reflux disease, with a primary gastrinoma of the common hepatic duct. The tumor was positive for a variety of immunohistochemical markers. Postoperatively the patient's symptoms disappeared and in the follow-up the patient was symptom free. To our knowledge, this is the first case in the literature of a primary gastrinoma in the common hepatic duct. The fact that the common hepatic duct is not located within the gastrinoma triangle made the diagnosis difficult and the distinct localization made the surgical treatment demanding.