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 long-term administration of neuroleptics causes tardive dyskinesia, which closely resembles levodopa-induced dyskinesias, and is brought about through complex mechanisms which are ill-defined. It is generally believed that the pathogenesis of tardive dyskinesia relates closely to the chronic blockade of dopamine receptor sites and that its pathophysiology results from a hypersensitivity of dopamine receptor sites. In the therapeutic management of neuroleptic-induced tardive dyskinesia, in addition to reserpine and lithium, diazepam, baclofen, or gamma-vinyl-gamma-aminobutyric acid have also been advocated. However, the reported beneficial effects of diazepam and GABA-mimetic agents in ameliorating the symptoms of tardive dyskinesia may occur through a mechanism which does not necessarily link transmission involving both dopamine and GABA. The presence of high concentrations of both cholecystokinin and opioids in the striatum also suggests that these peptides not only may influence dopaminergic transmission, but that they may also be relevant to the psychopathology of schizophrenia and to the therapeutic effects of neuroleptics. Indeed, the acute and chronic administration of neuroleptics alters the levels of cholecystokinin and opioids and their receptors in several brain regions including the striatum. However, neuroleptics also alter the biochemical integrity of neurotensin, neuropeptide Y, substance P and somatostatin, which may also play a role in the overall expression of the neuroleptic-induced extrapyramidal reactions.
 ...
PMID:Dopamine, GABA, cholecystokinin and opioids in neuroleptic-induced tardive dyskinesia. 290 20

Huntington disease is an autosomal dominant disorder that usually begins in mid-life and is characterized by progressive choreiform movements and dementia. Approximately 5% of patients develop symptoms prior to 14 years of age. In most juvenile cases, the gene is transmitted from the father. In children the clinical course is marked by mental deterioration or behavioral abnormalities, gait disturbances usually the consequence of rigidity, cerebellar signs, and seizures. The pathologic findings are highlighted by atrophy of the caudate. Atrophy also is observed on brain imaging, while positron emission tomography demonstrates marked caudate hypometabolism which antedates the appearance of the clinical disease. Cell death in the striatum primarily affects medium and small GABA-containing neurons, representing the striatal output projections. Somatostatin-containing neurons and cholinergic neurons are spared. The gene for Huntington disease has been localized in close proximity to the tip of the short arm of chromosome 4. The gene product and the manner by which it induces selective cell death is still unknown but should become evident in the near future.
 ...
PMID:Huntington disease: finding the gene and after. 297 83

Localized intracerebral microinjections of GABA, muscimol, picrotoxin and bicuculline were made in the anterior and basal hypothalamus to determine possible sites of action of GABA in the regulation of prolactin and growth hormone (GH) secretion. Studies were carried out in unanesthetized male rats with chronic indwelling atrial cannulae and intracerebral guide cannulae which permitted stress free blood sampling and intrahypothalamic injections, respectively. Preoptic/anterior hypothalamic area. (PO/AHA) injection of muscimol (0.16 nmol) stimulated both prolactin and GH secretion. GABA (1600 nmol) stimulated prolactin. Bicuculline (0.016 and 0.16 nmol) inhibited GH secretion. Medial basal hypothalamic (MBH) injection of muscimol (0.1 and 1.0 nmol) and GABA (1000 nmol) stimulated prolactin but had no effect on GH secretion. Picrotoxin and bicuculline did not stimulate GH. These findings indicate that activation of PO/AHA GABAergic receptors facilitates secretion of GH and prolactin and activation of MBH GABAergic receptors stimulates secretion of prolactin. It is proposed that GABA inhibits somatostatin neurons in the PO/AHA to facilitate GH and inhibits tuberoinfundibular dopamine or GABA neurons in the MBH to stimulate prolactin.
 ...
PMID:Activation of GABA receptors in the hypothalamus stimulates secretion of growth hormone and prolactin. 301 63

Immunocytochemical methods were used to localize tachykinin-like immunoreactivity within neurons of the monkey cerebral cortex. Three primary antibodies were used: polyclonal antisera raised against fragments of substance P and substance K that excluded the carboxyl termini of these peptides, and a monoclonal antibody that recognized the carboxyl terminus of the tachykinin family. Each antibody stained 2 populations of cortical nonpyramidal neurons: (1) A small number of large, intensely stained cells that give rise to long, coarsely beaded processes; (2) a relatively large number of small, lightly stained cells that are embedded in dense plexuses of stained punctate profiles. The large, dark cells are present in a superficial band that includes layers II and III, and in a deep band that includes layer VI and the subjacent white matter. The smaller, pale cells are present in the middle layers of cortex (layers IV and/or V). Colocalization studies indicate that virtually all the small tachykinin-immunoreactive neurons also display GABA immunoreactivity. The larger cells are not GABA-positive, but display both somatostatin-like and neuropeptide Y-like immunoreactivity. The immunocytochemically stained beaded processes and punctate profiles from plexuses that vary in density and laminar distribution among different areas of monkey cortex. The coarsely beaded processes form a basic quadrilaminar pattern, with relatively dense plexuses in layers I and VI and in 2 middle layers, usually III and V. However, this pattern varies considerably from area to area. Electron microscopically, the large cells contain a rich collection of cytoplasmic organelles, particularly Golgi complex, while the small cells contain relatively few organelles. Both types of cells, including large neurons in the white matter, receive symmetric and asymmetric synaptic contacts on their somata and proximal dendrites. The numbers of these axosomatic contacts are low. Virtually all synaptic contacts formed by immunoreactive terminals possess symmetric membrane thickenings. In 2 areas examined in detail (areas 2 and 4), pyramidal cell somata and dendrites are the major targets of the immunoreactive synaptic terminals.
 ...
PMID:A study of tachykinin-immunoreactive neurons in monkey cerebral cortex. 316 46

The El (epileptic) mouse is a model of hereditary sensory precipitated temporal lobe epilepsy. We compared vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI), somatostatin-like immunoreactivity (SS-LI), and gamma-aminobutyric acid-like immunoreactivity (GABA-LI) in the mid-hippocampal region of El and C57BL/6 mice. Specific interneuron populations with VIP-LI and GABA-LI were elevated in the El mice, whereas SS-LI populations were unchanged. These neurochemical alterations may be contributing to the epileptic predisposition of El mice.
 ...
PMID:VIP-, SS-, and GABA-like immunoreactivity in the mid-hippocampal region of El (epileptic) and C57BL/6 mice. 321 26

The onset of therapeutic effectiveness of carbamazepine is generally very rapid in the treatment of seizure and paroxysmal pain disorders, shows some lag in the treatment of mania, and exhibits the longest lag in depression. These time course variations may indicate that different mechanisms underlie the efficacy of carbamazepine in the differential neuropsychiatric syndromes. Biochemical and pharmacological data suggest that the anticonvulsant effects of carbamazepine are related to "peripheral-type" benzodiazepine and alpha 2-noradrenergic receptor systems and to its ability to stabilize sodium channels. GABAB (baclofen-like) actions appear to be involved in antinociceptive, but not anticonvulsant, effects. The relatively acute time course of antimanic efficacy may be related to the above-mentioned mechanisms or to other effects related to systems postulated to be altered in the manic syndrome. These effects might include carbamazepine's ability to increase acetylcholine in the striatum, decrease probenecid-induced levels of CSF homovanillic acid (HVA) in man and dopamine turnover in animals, decrease CSF norepinephrine in manic patients, inhibit adenylate cyclase activity (in response to norepinephrine, dopamine, adenosine, or ouabain), decrease GABA turnover, or act as a vasopressin agonist. Efficacy in depression may be related to actions in man that take time or chronic drug administration to develop, such as increases in plasma tryptophan, decreases in CSF somatostatin, decreases in thyroid indices, and increases in urinary free cortisol excretion and, in animals, increases in substance P sensitivity and increases in brain adenosine receptors. The ability of carbamazepine to block the development of lidocaine- and cocaine-induced seizures also requires chronic administration, suggesting that these seizure models may provide a unique perspective for understanding mechanisms of time-dependent effects.
 ...
PMID:Time course of clinical effects of carbamazepine: implications for mechanisms of action. 328 May 60

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


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