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 anticonvulsant action of the new anticonvulsant drug gamma-vinyl-GABA (GVG) is obviously mediated by elevation of the concentration of GABA in the brain. The effect of GVG administration on other transmitter systems is not fully known in humans. We studied the possible interactions of GVG administration with peptidergic systems. Included in this study were 67 patients with complex partial epilepsy (CPS). The first CSF sample was taken before GVG administration. The second CSF sample was taken after 3 months of GVG treatment (3 g/day). Thereafter half of the responders (50% decrease in seizure frequency or clear improvement in global performance) received 3 g/day and the other half received 1.5 g/day for the next three months, after which the third CSF sample was taken. Somatostatin (SLI), beta-endorphin (beta-EP), and prolactin (PROL) levels in CSF were measured by radioimmunoassay. Total GABA (tGABA) and GVG levels in CSF were measured by high performance liquid chromatography. After 3 months of GVG treatment there was a slight increase in the beta-EP (p = 0.027, Student's paired t-test), which was not found after 6 months of GVG administration. Both SLI and PROL were stable during the study. Peptide levels were not connected to the clinical response to GVG, GVG dosage, or to tGABA levels in the CSF. In conclusion, the elevation of GABA levels in the brain during GVG treatment apparently does not induce long-term interactions with the peptidergic systems studied.
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PMID:Somatostatin, beta-endorphin, and prolactin levels in human cerebrospinal fluid during the gamma-vinyl-GABA treatment of patients with complex partial epilepsy. 288 76

Remarkable progress has been made during recent years in the central regulation of the hypothalamic releasing and inhibiting factors and the respective anterior pituitary hormones. There are two nearly universal inhibitory organizations: short tuberoinfundibular dopamine (TIDA) neurons and somatostatinergic system originating from the periventricular hypothalamus and terminating to the median eminence. It is now known that e.g. dopamine, noradrenaline and acetylcholine enhance while 5-hydroxytryptamine and GABA inhibit somatostatin secretion. These transmitters are also involved in the regulation of all releasing factors and pituitary hormones. Clinical applications have been developed based on the regulation of prolactin and growth hormone. Inhibitory TIDA neurons are undoubtedly the major determinants of prolactin secretion. Hyperprolactinaemia is one of the most common endocrinological side-effects of the drugs antagonizing dopaminergic transmission. Expectedly, dopaminergic drugs (bromocryptine, lergotrile, piribedil, dopamine and levodopa) are quite effective in reducing high prolactin levels regardless of the reason. The secretion of growth hormone is predominantly under dual dopaminergic control: hypothalamic stimulation and pituitary inhibition. The former masters the function of the normal gland, while the peripheral inhibitory component takes over in acromegalic gland. Hence dopaminergic drugs are able to reduce elevated growth hormone levels in 30-50% of the acromegalic patients. In normal man, dopamine agonists increase growth hormone levels. An analogous situation can be seen in Cushing's disease regarding ACTH secretion.
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PMID:Aminergic regulation of neuroendocrinological functions: theoretical background and some clinical examples. 288 29

Somatostatin-immunoreactive perikarya in the periventricular anterior hypothalamus were demonstrated to be surrounded by gamma aminobutyric acid GABA-immunoreactive nerve terminals, by combining pre-embedding immunocytochemistry for somatostatin and gold labelling post-embedding immunocytochemistry for GABA. Ultrastructural studies revealed that in each 100-nm section, cells immunoreactive for somatostatin (n = 62) were contacted by a mean of 7.6 +/- 0.4 terminal profiles of which 3.0 +/- 0.3 (40%) were GABA-immunoreactive. Most GABA-immunoreactive terminals contained clear rounded vesicles and, where synaptic specializations were well demonstrated, appeared to be symmetric. The finding provides evidence that there is a significant GABA input to somatostatin neurons, an observation strengthening the hypothesis that GABA may inhibit somatostatin neurons, thereby causing increased secretion of growth hormone.
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PMID:Ultrastructural evidence for gamma aminobutyric acid-immunoreactive synapses on somatostatin-immunoreactive perikarya in the periventricular anterior hypothalamus. 288 53

Fetal parietal cerebral cortex was transplanted to the anterior eye chamber of adult Sprague-Dawley rats. After two to three months the grafts, with or without colchicine treatment, were subjected to immunohistochemical analysis using antibodies against cholecystokinin (CCK), somatostatin (SOM), neuropeptide tyrosine (NPY), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI) and the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). Cerebral cortex in situ of untreated and colchicine-treated rats was always analyzed in parallel. A dense plexus of CCK-immunoreactive fibers was distributed in all parts of the transplants, and after colchicine treatment a large number of CCK-positive cells was observed. These cells were markedly increased in number as compared to normal cortical tissue in colchicine-pretreated rats. The amount of NPY-immunoreactive cells was also markedly increased, whereas somatostatin-positive cells were found in numbers similar to those seen in cortex in situ. In the grafts only a few VIP- and PHI-positive fibers were seen with a few VIP-positive cell bodies, but no clearly discernible PHI-positive cells. A very dense plexus of GAD-positive fibers with an even distribution throughout the grafts was observed. Cortex in situ exhibited a lower density of GAD-immunoreactive fibers. Even after colchicine treatment the number of GAD-positive cells in the grafts was low. Using double-staining techniques, it was found that most of the few GAD-positive cells in the grafts were also NPY-positive, SOM-positive or, to a minor extent, CCK-positive. The present results demonstrate that several peptides and transmitter markers are expressed in cortical grafts in oculo, but marked differences in their expression can be observed in cortical tissue that has developed in isolation. Thus, the intraocular cortex graft, alone and in combination with other brain areas, should provide a useful model in which to study factors that regulate brain development.
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PMID:Glutamic acid decarboxylase- and peptide-immunoreactive neurons in cortex cerebri following development in isolation: evidence of homotypic and disturbed patterns in intraocular grafts. 290 91

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.
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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.
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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.
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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.
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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.
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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.
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PMID:Time course of clinical effects of carbamazepine: implications for mechanisms of action. 328 May 60


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