Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biochemical assays on microdissected samples, denervation studies, subcellular fractionation, and light and electron microscopic autoradiography of high affinity uptake have been performed to study the cellular localization of transmitter candidates in the rat hippocampal formation. High affinity uptake of glutamate and aspartate is localized in the terminals of several excitatory systems, such as the entorhino-dentate fibres (perforant path), mossy fibres (from granular cells) and pyramidal cell axons. Thus, in stratum radiatum and oriens of CA1, 85% of glutamate and asparate uptake and 40% of glutamate and aspartate content are lost after lesions of ipsilateral plus commissural fibres from CA3/CA4. Hippocampal efferents also take up aspartate and glutamate, since these activities are heavily reduced in the lateral septum and mamillary bodies after transection of fimbria and the dorsal fornix. The synthesis (by glutamic acid decarboxylase), content and high affinity uptake of gamma-aminobutyrate (GABA) are not reduced after lesions of these or other projection fibre systems. A localization in intrinsic neurons is confirmed by a selective loss of glutamic acid decarboxylase after local injections of kainic acid. Peak concentrations of the enzyme occur near the pyramidal and granular cell bodies, corresponding to the site of the inhibitory basket cell terminals, and in the outer parts of the molecular layers. Some 85% of glutamic acid decarboxylase is situated in 'nerve ending particles'. Acetylcholine synthesis (by choline acetyltransferase) disappears after lesions of septo-hippocampal fibres. Since 80% of the hippocampal choline acetyltransferase is in 'nerve ending particles', the characteristic topographical distribution of this enzyme should reflect the distribution of cholinergic septo-hippocampal afferents. Serotonin, noradrenaline, dopamine and histamine are located/synthesized in afferent fibre systems. Some monoamine-containing afferents to the hippocampal formation pass via the septal area, others via the amygdala. The hippocampal formation also contains nerve elements reacting with antibodies against neuroactive peptides, such as enkephalin, substance P, somatostatin and gastrin/cholecystokinin.
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PMID:Localization of putative transmitters in the hippocampal formation: with a note on the connections to septum and hypothalamus. 3 19

Huntington's disease is a progressive neurodegenerative disease in which the basal ganglia are preferentially affected. Recent evidence, however, suggests involvement of the cerebral cortex as well, with sparing of neurochemically defined subsets of gamma-aminobutyric acid (GABA)-ergic interneurons. In the present study, we examined changes in concentrations of the amino acid neurotransmitters GABA, glutamate, and aspartate in nine cortical regions from 23 patients with advanced Huntington's disease and 12 control brains. GABA concentrations were significantly increased in eight of the nine regions, consistent with a sparing of GABAergic local circuit neurons in the context of progressive cortical atrophy. Small but significant increases in glutamate were found in six of the nine regions, while aspartate levels were generally unaffected. Striate cortex (Brodmann's area 17) showed the most profound increases in GABA and glutamate. We also investigated the effects of powdering the excitotoxins N-methyl-D-aspartate (NMDA) or kainic acid onto the dura of rats. The resulting lesions were examined at 1 week and 6 months. The NMDA-induced lesions showed striking sparing of parvalbumin-positive neurons (a subset of GABAergic interneurons), and this sparing was reflected in neurochemical measurements of GABA; kainic acid lesions failed to display this selectivity. Somatostatin, cholecystokinin, and vasoactive intestinal polypeptide concentrations were spared by the NMDA-induced lesions, and substance P levels were significantly increased. These results provide evidence that NMDA excitotoxic lesions of cerebral cortex can produce a selective pattern of neuronal damage similar to that which occurs in Huntington's disease.
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PMID:The cortical lesion of Huntington's disease: further neurochemical characterization, and reproduction of some of the histological and neurochemical features by N-methyl-D-aspartate lesions of rat cortex. 128 Sep 37

Recent studies have provided new data on the neuroendocrine role of glutamate (the major excitatory neurotransmitter) on somatostatin release. The neuroendocrine role of gamma-aminobutyric acid (GABA) (the major inhibitory neurotransmitter) on this same secretion, is also well established. Our objective was thus to investigate whether GABA and glutamate, which have opposite neurotransmission signals, could interact in the control of hypothalamic somatostatin release. Pharmacological manipulations of the two types of receptors were performed in vitro on primary cultures of hypothalamic neurons secreting somatostatin. We found that tonic release of somatostatin was reduced by 76% in the presence of tetrodotoxin (TTX) and was regulated by endogenous secretion of glutamate and GABA. CGS 19755, a highly selective N-methyl-D-aspartate (NMDA) receptor antagonist, significantly reduced tonic somatostatin secretion whereas it was strongly increased by picrotoxin and bicuculline, two GABAA antagonists. When CGS 19755 was applied with picrotoxin, somatostatin release was the same as levels obtained in the control group with TTX. GABA reduced tonic somatostatin release (in the presence or absence of TTX), and glutamate-stimulated secretion in a dose-dependent manner. Picrotoxin stimulation of tonic somatostatin release was additive with that obtained after glutamate stimulation and was also dose-dependent. This interaction was also studied in vivo in unanesthetized rats bearing a push-pull cannula stereotaxically implanted into the median eminence. Ip injected CGS 19755 (an antagonist that can freely permeate the blood-brain barrier) completely blocked the peak secretion of somatostatin observed after ip picrotoxin administration, whereas there was no significant effect when it was injected alone. These findings corroborated our in vitro data and allow us to postulate that GABA and glutamate interact in the control of somatostatin.
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PMID:Gamma-aminobutyric acid-glutamate interaction in the control of somatostatin release from hypothalamic neurons in primary culture: in vivo corroboration. 134 78

Several neurotransmitters have been reported to exist in the ganglionated plexus of the guinea pig gallbladder. These include substance P, neuropeptide Y (NPY), calcitonin gene-related peptide, vasoactive intestinal peptide (VIP), acetylcholine, norepinephrine, serotonin, and dopamine. To determine which neuropeptides are intrinsic to gallbladder ganglia, we performed immunohistochemistry on colchicine-treated preparations. In separate, single-labeled preparations, a majority of neurons contained substance P-, NPY-, or somatostatin-like immunoreactivity. In double-labeled preparations, a large majority of the neurons that contained substance P-like immunoreactivity also contained NPY-like immunoreactivity and somatostatin-like immunoreactivity. Immunoreactivity for VIP was present in a small percentage of the gallbladder neurons which did not contain substance P-like immunoreactivity. Additional experiments were done to test for the presence of other compounds, known to exist in the neurons of the gut. Although immunoreactivity was found in control preparations of small intestine, the ganglionated plexus of the gallbladder lacked immunoreactivity for galanin, dynorphin, enkephalin, gastrin-releasing peptide, or gamma-aminobutyric acid. We conclude that ganglia of the guinea pig gallbladder contain at least two populations of neurons, based on transmitter phenotype. One of these populations appears to contain substance P, NPY, and somatostatin. Another population, which represents a small contingent of the total population of neurons, contains VIP.
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PMID:Transmitter diversity in ganglion cells of the guinea pig gallbladder: an immunohistochemical study. 134 12

The role of specific neuronal populations in epileptic foci was studied by comparing epileptic and non-epileptic cortex removed from patients with low-grade gliomas. Epileptic and nearby (within 1 to 2 cm) non-epileptic temporal lobe neocortex was identified using electrocorticography. Cortical specimens taken from four patients identified as epileptic and nonepileptic were all void of tumor infiltration. Somatostatin- and gamma-aminobutyric acid (GABAergic)-immunoreactive neurons were identified and counted. Although there was no significant difference in the overall cell count, the authors found a significant decrease in both somatostatin- and GABAergic-immunoreactive neurons (74% and 51%, respectively) in the epileptic cortex compared to that in nonepileptic cortex from the same patient. It is suggested that these findings demonstrate changes in neuronal subpopulations that may account for the onset and propagation of epileptiform activity in patients with low-grade gliomas.
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PMID:Changes in gamma-aminobutyric acid and somatostatin in epileptic cortex associated with low-grade gliomas. 135 40

Neuroanatomical data have documented the existence of synaptic contacts between gamma-aminobutyric acid (GABA) terminals and periventricular hypothalamic somatostatin (SRIF) neurons. In other brain regions, like the cortex or hippocampus, GABA and SRIF are colocalized in short interneurons. These observations suggest that GABA modulates SRIF neuronal activity. In order to test this hypothesis, we studied the effects of the in vivo stimulation of the GABAA receptor (muscimol, 0.75 mg/kg + diazepam, 2.5 mg/kg) on SRIF content and preproSRIF mRNA levels, in mouse brain. Chronic (7 days), but not acute, treatment induced a 38% decrease in hypothalamic SRIF content (as estimated by RIA), a 20% decrease in cortex and no effect in the striatum. The decrease in hypothalamic and cortical SRIF levels lasted until 24 h after cessation of the treatment. In the hypothalamus, prosomatostatin mRNA levels were estimated by Northern blot analysis using a 32P-labeled 45-mere oligoprobe. ProSR1F mRNA hypothalamic levels were equally (48%) decreased by the acute and chronic treatments and remained lower than controls 48 h after the last injection. Quantitative in situ hybridization was used to examine the regional distribution of GABA-induced acute inhibition of proSR1F mRNA densities, using the same oligomere labeled with 35S. ProSR1F mRNA levels were decreased by 35% in the periventricular hypothalamic nucleus. In contrast, no significant modification was observed in cortex, striatum and hilus of the dentate gyrus of the dorsal hippocampus. The present data demonstrate a regionally selective inhibitory action of GABA, mediated by GABAA receptors stimulation, on the biosynthetic mechanisms of the long projecting neuroendocrine SRIF neurons of the anterior periventricular nucleus of the hypothalamus.
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PMID:Regulation of somatostatin synthesis by GABAA receptor stimulation in mouse brain. 135 11

Calretinin and calbindin-D28k are two calcium-binding proteins which are present in separate populations of interneurons in cerebral cortex and hippocampus. To identify these cells with the populations expressing different transmitters, two-colour immunofluorescence was done with antibodies against the calcium-binding proteins plus antibodies against vasoactive intestinal peptide (VIP), somatostatin (SRIF), or gamma-aminobutyric acid (GABA). In neocortex, calretinin is partially co-localized with VIP (especially in the deeper layers) and is not co-localized with SRIF. Calbindin is largely co-localized with SRIF, and not with VIP. Both calretinin and calbindin are partially co-localized with GABA. In piriform and entorhinal cortex, the patterns resemble those in neocortex. In hippocampus, preliminary data indicate greater heterogeneity, especially in the ventral part; at least a few double-positive cells are present for every combination of calcium-binding protein and neuropeptide. These results expand the known diversity of local-circuit neurons in cortical regions.
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PMID:Immunohistochemical markers in rat cortex: co-localization of calretinin and calbindin-D28k with neuropeptides and GABA. 135 60

Somatostatin and gamma-aminobutyric acid (GABA) are co-localized in some neurons in the CA1 area of the hippocampus. Since it is possible that the peptide and the amino acid are co-released, the interactions between the actions of somatostatin and GABA-ergic inhibitory post-synaptic potentials (IPSPs) in the CA1 pyramidal neurons of guinea pig hippocampal slices have been investigated. Somatostatin (2 microM) induced a hyperpolarization of the CA1 neurons associated with a reduction in the input resistance of the cells. These effects were not blocked by picrotoxinin (20 microM) or phaclofen (1 mM). Chelation of intracellular Ca2+ (Ca2+i) with BAPTA or the inhibition of protein kinase C (PKC) with sphingosine (30 microM) had no significant effects on the hyperpolarizing actions of somatostatin. The peptide suppressed the GABAA receptor-mediated fast IPSPs and the GABAB receptor-mediated slow IPSPs, but had no significant effect on the excitatory post-synaptic potentials (EPSPs). Somatostatin-induced depression of the IPSPs was not due to the hyperpolarization of the neurons. Baclofen (20 microM) suppressed the EPSP, as well as the fast and the slow IPSPs. The hyperpolarization of the CA1 neurons caused by somatostatin was greatly reduced in the presence of baclofen, an effect that was not due to the hyperpolarization of the cell by baclofen. The presence of QX-314 in the CA1 neurons, which suppressed the Na+ spikes and the slow IPSPs, prevented the hyperpolarization of the neurons by somatostatin and baclofen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Actions of somatostatin on GABA-ergic synaptic transmission in the CA1 area of the hippocampus. 135 22

Postsynaptic targets of the GABAergic septohippocampal and the serotonergic raphe-hippocampal pathways were studied using anterograde tracing with Phaseolus vulgaris leucoagglutinin combined with pre- and postembedding immunocytochemistry in the rat. Two types of afferents were labeled in the hippocampus and dentate gyrus from the medial septum-diagonal band of Broca complex, one with large diameter varicosities and another with smaller terminals. The former type was shown to be immunoreactive for gamma-aminobutyric acid (GABA), and to innervate predominantly GABA-immunoreactive interneurons. Subsequently, these target interneurons were demonstrated to include all subpopulations of GABAergic cells which could be visualized by antisera against parvalbumin, calbindin D28k, calretinin, cholecystokinin, somatostatin, neuropeptide Y and vasoactive intestinal polypeptide. These types of interneurons have different afferent and efferent connections, and thus participate in different inhibitory processes in the hippocampal formation. The other subcortical pathway, the serotonergic projection from the median raphe nucleus, was also shown to establish synapses predominantly with GABAergic interneurons both in the hippocampus and in the dentate gyrus. In contrast to the septohippocampal projection, this pathway did not innervate all types of GABAergic neurons. They selected a particular subpopulation, i.e. those which contain calbindin D28k, and ignored those which contained parvalbumin or the other neurochemical markers. This suggests a strong functional specialization among local inhibitory circuits, as well as among the subcortical afferents originating in the septum and raphe. These findings suggest that a mechanism by which numerically small afferent pathways may have a profound global effect on the electrical activity of the hippocampal formation is the selective innervation of local interneurons. These GABAergic inhibitory cells, in turn, control the activity of large populations of principal cells. The level of GABAergic inhibition determines the degree of population synchrony and influences N-methyl-D-aspartate receptor-mediated epileptiform burst-firing. Thus, the specific subcortical modulation of hippocampal inhibitory circuits may also have fundamental implications for epileptogenesis.
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PMID:GABAergic septal and serotonergic median raphe afferents preferentially innervate inhibitory interneurons in the hippocampus and dentate gyrus. 136 33

The thalamic reticular nucleus has been classically defined as a group of cells surrounding most of the rostral and lateral surfaces of the dorsal thalamus, lateral to the fibres of the external medullary lamina and medial to those of the internal capsule. With the use of Nissl staining and antibodies to gamma-aminobutyric acid (GABA), somatostatin, and parvalbumin, this study describes the cytoarchitecture of the thalamic reticular nucleus of cats and ferrets. In cats, three subdivisions of the nucleus are distinguished, two of which are distinct in ferrets also. First, the main body of the reticular nucleus lies lateral to the fibres of the external medullary lamina (except ventrally) and medial to those of the internal capsule. In both cats and ferrets, this structure is heterogeneous, consisting of distinct layers, the details of which vary along the dorsoventral axis. A prominent rostroventral portion of comparatively small rounded cells is also apparent within the main body. Most reticular cells in all areas of the main body are labelled with all of the above mentioned antibodies. Second, the inner small-celled region is a group of small cells located between the external medullary lamina (ventrally) and the medial margin of the ventral regions of the main body of the reticular nucleus: the inner small-celled region is clearly differentiated in cats only. Previous studies have referred to this area as being part of the main body of the reticular nucleus, but we suggest that it may form a separate subnucleus. For example, the inner small-celled region stands in striking contrast to the main body of the reticular nucleus in that none of its cells are GABA immunoreactive and only a small caudal subpopulation are parvalbumin immunoreactive. A very similar pattern of immunostaining is apparent for the cells in the zona incerta, although the latter contains a small rostral subpopulation of GABA immunoreactive cells. Furthermore, although morphologically distinct from the zona incerta, the inner small-celled region fuses with it ventrocaudally. We suggest that the inner small-celled region may constitute a previously undescribed dorsal extension of the zona incerta, rather than a subdivision of the reticular nucleus. Third, the perireticular nucleus, hitherto unidentified, is a discrete group of small cells lateral to the main body of the reticular nucleus and medial to the corpus striatum (globus pallidus and caudate-putamen). It is apparent throughout most of the dorsoventral extent of the main body of the reticular nucleus of cats and ferrets.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytoarchitectonic heterogeneities in the thalamic reticular nucleus of cats and ferrets. 138 30


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