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

The GABAergic properties of dissociated neurons from cerebral cortex of neonatal rats were studied in primary culture using electrophysiological, biochemical and immunohistochemical methods. Cultured neurons had a resting potential of -50 to -60 mV and exhibited spontaneous excitatory and inhibitory synaptic currents. Non-spontaneous (elicited) ionic currents were produced by direct application of GABA and glutamate. Cultures contained measurable amounts of GABA from the first day in culture; GABA content reached a plateau around the 10th day of culture, and continued, nearly unchanged, until the 21st day of culture. Immunohistochemistry showed that 45% of the total cells in culture contained glutamic acid decarboxylase (GAD). Octadecaneuropeptide (ODN), a putative neuroregulatory peptide for benzodiazepine recognition sites, was present in approximately 28% of all neurons. Ninety-three percent of ODN-positive cells demonstrated GABAergic properties as well by displaying GAD-immunoreactivity. The peptide GABA-modulin (GM), a putative GABA receptor modulator, was found in about 75% of all neurons, with a further 65% of these cells exhibiting GAD-immunoreactivity. Cells immunopositive for neuropeptide Y (NPY), somatostatin (SRIF), and cholecystokinin-octapeptide (CCK), were found at much lower incidence (1-4%). Double-labelling studies showed that 90-97% of the cells positive for NPY, SRIF and CCK were also positive for GAD. Cells immunoreactive with serotonin or tyrosine hydroxylase were not detected. We suggest that primary cultures of neonatal cortical neurons may provide a useful experimental model to investigate the function and the modulation of GABAergic neurotransmission in the cerebral cortex.
 ...
PMID:Subsets of GABAergic neurons in dissociated cell cultures of neonatal rat cerebral cortex show co-localization with specific modulator peptides. 337 69

Alzheimer's disease of early onset versus that of late onset represent different syndromes, with distinct neuropathologies. Patients with early onset disease exhibit a more severe and more widespread loss of neurons from cortical and sub-cortical regions and the neurochemical changes involve not only the cholinergic system, but also neurons containing GABA, somatostatin and norepinephrine.
 ...
PMID:Differences between early and late-onset Alzheimer's disease. 343 30

Since neuroimmunomodulation is brought about in part, at least, by secretion of pituitary hormones involved in stress and immune responses, we review briefly the hypothalamic control of the release of ACTH, growth hormone, and prolactin. The release of ACTH is controlled particularly by corticotropin-releasing factor (CRF), but vasopressin has intrinsic releasing activity and potentiates the action of CRF at both hypothalamic and pituitary levels. Oxytocin may even potentiate the action of CRF, but has little, if any, ACTH-releasing activity by itself. In addition, epinephrine may augment responses to the CRFs. In contrast, growth hormone is under dual control by growth-hormone-releasing factor (GRF) and somatostatin, and prolactin is under multifactorial control by a series of inhibitors and stimulators. Dopamine is accepted as a physiological prolactin-inhibiting factor (PIF), but probably GABA and possibly acetylcholine as well are PIFs. There is good evidence for a peptide PIF as well. There are a number of prolactin-releasing factors (PRFs) which include oxytocin, vasoactive intestinal polypeptide, PHI and TRH. Several other peptides can also release prolactin, including angiotensin II. In response to stress there is a complex interaction of peptides intrahypothalamically. CRF augments its own release by an ultra short-loop positive feedback, and there is negative ultra short-loop feedback of GRF and somatostatin. Vasopressin appears to augment CRF release as well as to act directly on the pituitary, and there are complex interactions of various peptides to influence prolactin and GH release.
 ...
PMID:The role of brain peptides in neuroimmunomodulation. 347 67

Hippocampal neurons containing GABA-, cholecystokinin(CCK)-, vasoactive intestinal polypeptide(VIP)-, or somatostatin(SS)-like immunoreactivity (LI) were localized in sections of rat hippocampus. GABA-, CCK-, VIP, and SS-LI are found exclusively in interneurons of the area dentata and hippocampus. In the area dentata, GABA-LI occurs in cells of all strata but predominates in type 1 and 2 basket cells. CCK-LI is present in a subset of these basket cells and some hilar cells. VIP-LI is present in a distinct subset of dentate interneurons that, unlike the type 1 and 2 basket cells, do not contribute to the fiber plexus in the inner molecular layer. These VIP-LI interneurons send their axons to nearby granule cells and form a plexus in the hilus. SS-LI, although rare in cells of the molecular and granular layers, is present in a large population of hilar interneurons that do not exhibit GABA-, CCK-, or VIP-LI. In area CA3 of the hippocampus, a variety of morphologically diverse interneurons containing GABA-, CCK-, VIP-, or SS-LI are present in all strata. In area CA1, SS-LI is present mainly in cells of strata oriens and pyramidale. GABA- CCK- and VIP-LI interneurons are present in all strata of CA1 but, unlike the SS-LI cells, are most numerous in strata pyramidale and radiatum. These findings in the area dentata, taken together with those of Kosaka et al. (J. Comp. Neurol. 239:967-969, '85), indicate that two main populations of interneurons can be discriminated on the basis of the substances they contain. One is a group of GABA-LI cells, some of which also contain CCK- and/or VIP-LI. These cells innervate the granule cells and the second group of interneurons, the SS-LI hilar cells, which apparently form part of the dentate ipsilateral associational/commissural projections.
 ...
PMID:Immunocytochemical localization of GABA-, cholecystokinin-, vasoactive intestinal polypeptide-, and somatostatin-like immunoreactivity in the area dentata and hippocampus of the rat. 381 38

Parkinson's disease is characterized by a deficiency of dopamine in the nigrostriatal system. However, changes in dopamine neurons were found also outside the extrapyramidal system, showing that there is a more general brain defect than just the loss of substantia nigra dopamine neurons. With regard to the behavior of striatal D-2 receptors it was possible to divide parkinsonian patients into two subgroups, because either a decrease or an increase in the number of D-2 receptors was found. Clinically, the patients with a decreased number of striatal D-2 receptors were more disabled and had lost the beneficial response to levodopa. D-3 receptor binding sites were decreased in the parkinsonian striatum. Changes in the cholinergic-muscarinic receptors in the striatum seem to be related to changes in D-2 receptors, and muscarinic receptor supersensitivity was found in cortical areas. GABA receptor binding was decreased in the substantia nigra. In the parkinsonian brain there seems to be supersensitivity of a population of enkephalin receptors (delta) in the striatum and in the limbic system and also a loss of others (mu) in the striatum. Furthermore, the Met-enkephalin content was decreased in the parkinsonian substantia nigra. A decreased concentration of substance P was found in the substantia nigra of all parkinsonian patients and in the putamen of those patients who had not received levodopa treatment. The somatostatin level was decreased in the frontal cortex in relation to dementia. There are thus multiple neuronal disturbances in the parkinsonian brain, although those of the nigrostriatal dopamine neurons seem to be the greatest and are more closely related to parkinsonian clinical features and to treatment responses.
 ...
PMID:Brain neurotransmitters and neuropeptides in Parkinson's disease. 609 88

Somatostatin (SRIF) was applied microiontophoretically to neurons in the frontal and parietal neocortex, the hippocampus and the striatum of rats anaesthetized with either urethane or chloral hydrate. Qualitatively identical results were obtained under both anaesthetic conditions. In urethane-treated rats SRIF elicited a dose-dependent increase of the firing rate of 74% of the neurons studied in the frontal cortex and of 46% of the neurons studied in the parietal cortex. All cortical cells identified as pyramidal cells were excited. In the hippocampus SRIF provoked excitatory responses in two thirds of all neurons. Six out of the nine cells identified as pyramidal cells were excited by SRIF. In the striatum 80% of all neurons were excited. Following repeated exposure of central neurons to SRIF, the magnitude of the excitatory response gradually diminished, indicating desensitisation. SRIF in concentrations ranging from 10(-8) to 10(-4) M did not interfere with the binding of (3H)-muscimol to GABA receptor sites. The release of GABA from synapses preloaded with (3H-GABA) was not influenced by SRIF in the concentration range from 10(-6) to 10(-4) M. These results indicated that SRIF does not evoke the excitatory responses through attenuation of GABA-mediated inhibition. In conclusion, the findings support the hypothesis that somatostatin may function as a neurotransmitter in the central nervous system.
 ...
PMID:Central actions of somatostatin. 610 12

Primary cultures of dispersed hypothalamic cells were prepared from embryonic rats to study the release of immunoreactive somatostatin. The immunoreactive somatostatin content of these cultures increased during the first 2 weeks after plating and was readily measurable for several weeks thereafter; this material was characterized by gel permeation and reverse-phase chromatography. Depolarization of the cells with 60 mM K+ or with veratridine resulted in a calcium-dependent release of immunoreactive somatostatin which cochromatographed with synthetic somatostatin on reverse-phase chromatography. Tetrodotoxin blocked the veratridine-evoked release. However, even in the absence of exogenous stimuli, immunoreactive somatostatin was released by the cells into the medium. More than 70% of this tonic release was found to be calcium dependent and to be inhibited by tetrodotoxin, indicating that spontaneous electrical activity in the cultures leads to a release of immunoreactive somatostatin. gamma-Aminobutyric acid inhibited the tonic release of immunoreactive somatostatin and this was reversed by bicuculline. These findings support the hypothesis that gamma-aminobutyric acid inhibits somatostatin release in vivo.
 ...
PMID:Release of immunoreactive somatostatin from hypothalamic cells in culture: inhibition by gamma-aminobutyric acid. 610 13

Neurotransmitter effects were studied on in vitro release of immunoreactive somatostatin (SRIF) from slices prepared from several regions of the rat brain: mediobasal hypothalamus (MBH), preoptic anterior hypothalamic area (POA) and amygdaloid complex (AMY). Potassium (K+, 56 mM) stimulated SRIF release in all structures tested in a calcium dependent manner. Morphine, dopamine, GABA and serotonin did not modify SRIF release in any structure; noradrenaline (NA) was not effective on MBH slices, but elicited a dose-dependent stimulation of SRIF release from POA and AMY (ED50 = 6.4 +/- 1.4 nM and 3.6 +/- 1.2 nM respectively). Converse orders of potency of adrenergic agonists were observed in both structures (POA, adrenaline greater than noradrenaline greater than isoproterenol; AMY, isoproterenol greater than adrenaline greater than noradrenaline). Phentolamine blocked NA-induced SRIF release in the POA while propranolol was ineffective. On the contrary, propranolol, but not phentolamine, antagonized NA stimulation in the amygdala. The data suggest that NA acting through specific receptors modulate SRIF release from POA and AMY. In POA, NA effect seems mediated through alpha adrenergic receptors while in AMY, beta receptors are involved. The possibility that these interactions of NA with SRIF release are correlated with effects of NA on growth hormone secretion or on epileptic events is discussed.
 ...
PMID:Noradrenaline stimulates somatostatin release from incubated slices of the amygdala and the hypothalamic preoptic area. 611 80

The influence of cortical neurotransmitters and cyclic AMP on the release of immunoreactive somatostatin (IRS)from cultured cortical cells was examined. Cells were obtained by mechanoenzymatic dispersal of telencephalons of 17-day-old rat embryos and were maintained as monolayers in minimum essential medium with 10% heat-inactivated horse serum. After the cultures had stabilized morphologically and in cellular IRS content they were subjected to rapid sequential changes of a buffered salt solution with or without test substances added. The amount of somatostatin released was measured by a specific radioimmunoassay. Acetylcholine and the GABA antagonist, picrotoxin, both stimulated IRS release. The cholinergic stimulation was predominantly muscarinic. GABA and histamine, to a lesser extent, were inhibitory and norepinephrine and serotonin produced no net change in IRS release. Both cAMP and theophylline (DMX) stimulated IRS release. These results confirm the potential of intrinsic cortical somatostatinergic neurons to respond to endogenous neurotransmitters and further establishes somatostatin as a cortical neuromodulator.
 ...
PMID:Effects of neurotransmitters and cyclic AMP on somatostatin release from cultured cerebral cortical cells. 612 Jul 48

gamma-Aminobutyric acid (GABA) is regarded as the major inhibitory neurotransmitter in the central nervous system of vertebrates. GABA exerts its inhibitory actions by interacting with specific receptors on pre- and postsynaptic membranes and has been shown to inhibit somatostatin release from hypothalamic neurones in vitro. Concepts of innervation of the gastrointestinal tract have been expanded by recent studies which suggest that GABAergic neurones are not confined solely to the central nervous system but may also exist in the vertebrate peripheral autonomic nervous system. Jessen and coworkers have demonstrated the presence, synthesis and uptake of GABA by the myenteric plexus of the guinea pig taenia coli, and have documented the presence of glutamic acid decarboxylase (GAD) in isolated myenteric plexus. This enzyme is responsible for the conversion of glutamic acid to GABA in GABAergic neurones. The possibility that GABA may have a role in neurotransmission or neuromodulation in the enteric nervous system of the vertebrate gut has been suggested by several investigators. Furthermore, GABA receptors have been demonstrated on elements of the enteric nervous system. The effects of GABA on gastrointestinal endocrine cell function have not been examined. We report here the effects of GABA on gastrin and somatostatin release from isolated rat antral mucosa in short-term in vitro incubations.
 ...
PMID:GABA affects the release of gastrin and somatostatin from rat antral mucosa. 613 39


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>