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 effects of short-term (90 min), mid-term (5 days), and long-term (15 days) administration of ammonium acetate (5 mmol/Kg day i.p.) on the somatostatinergic neurotransmitter system of the rat hippocampus have been studied. Scatchard analysis of the binding of 125I-Tyr11-somatostatin to hippocampal dissociated cells indicated that administration of ammonium acetate at the times studied were associated with a decrease in the number of somatostatin receptors in this brain area, whereas the affinity of the same receptors remained unchanged. Administration of ammonium acetate did not affect the levels of somatostatin-like immunoreactivity in the hippocampus. Treatment with N-carbamyl-L-glutamate (1 mmol/Kg, i.p.) plus L-arginine (1 mmol/kg), which lead to the conversion of ammonia into urea, prevented the ammonium acetate-induced changes in somatostatin binding in this brain area. N-carbamyl-L-glutamate plus L-arginine alone had no observable effect on the somatostatinergic system. The decrease in the number of somatostatin receptors induced by ammonium acetate might reflect a decreased sensitivity of the target cells to somatostatin, a phenomenon that could contribute to the depressed neuronal excitability induced by ammonia in the rat hippocampus.
 ...
PMID:Somatostatin binding reduced by ammonium acetate in the rat hippocampus can be reversed by treatment with N-carbamyl-L-glutamate plus L-arginine. 135 63

Glutaminase has been considered to be a synthesizing enzyme of transmitter glutamate in pyramidal neurons of the cerebral cortex. In the present study, an attempt was made to examine with a double immunofluorescence method whether or not nonpyramidal neurons of the cerebral cortex are immunoreactive for glutaminase. Glutaminase was stained with mouse anti-glutaminase IgM and FITC-labeled anti-[mouse IgM] antibody. In the same section, parvalbumin (PA), calbindin (CB), choline acetyltransferase (CAT), vasoactive intestinal polypeptide (VIP), corticotropin releasing factor (CRF), cholecystokinin (CCK), somatostatin (SS), or neuropeptide Y (NPY) was visualized as a marker for nonpyramidal neurons with an antibody to each substance, biotinylated secondary antibody and Texas Red-labeled avidin. Virtually no glutaminase immunoreactivity was seen in PA-, CB-, CAT-, VIP-, CRF-, CCK-, SS-, or NPY-immunoreactive neuronal perikarya in the neocortex and mesocortex (cingulate and retrosplenial cortices), although it was detected in a few PA-, CB-, VIP-, CCK-, SS-, or NPY-immunoreactive nonpyramidal neurons in the piriform, entorhinal, and hippocampal cortices. PA- and CB-positive neurons have been reported to constitute the major population of GABAergic neurons in the cerebral cortex. Thus, the present results, together with the previous reports, suggest that most GABAergic, cholinergic and peptidergic nonpyramidal neurons in the neo- and mesocortex do not contain glutaminase.
 ...
PMID:Paucity of glutaminase-immunoreactive nonpyramidal neurons in the rat cerebral cortex. 138 31

This paper reviews chemical models of epilepsy and their relevance in the identification and characterization of anticonvulsants. For each convulsant we discuss possible modes of administration, clinical type(s) of seizures induced, proposed mechanism(s) of epileptogenesis and, where available, responsiveness of the induced seizures to anticonvulsants. The following compounds are reviewed: pentylenetetrazol, bicuculline, penicillin, picrotoxin, beta-carbolines, 3-mercaptopropionic acid, hydrazides, allylglycine; the glycine antagonist strychnine; gamma-hydroxybutyrate; excitatory amino acids (glutamate, aspartate, N-methyl-D-aspartate, quisqualate, kainate, quinolinic acid); monosubstituted guanidino compounds, metals (alumina, cobalt, zinc, iron); neuropeptides (opioid peptides, corticotropin releasing factor, somatostatin, vasopressin); cholinergic agents (acetylcholine, acetylcholinesterase inhibitors, pilocarpine); tetanus toxin; flurothyl; folates; homocysteine and colchicine. Although there are a multitude of chemical models of epilepsy, only a limited number are applied in the routine screening of potential anticonvulsants. Some chemical models have a predictive value with regard to the clinical profile of efficacy of the tested anticonvulsants. Some chemical models may contribute to a better understanding of possible mechanisms of epileptogenesis.
 ...
PMID:Chemical models of epilepsy with some reference to their applicability in the development of anticonvulsants. 139 44

Multiple neuroreceptor changes are present in Alzheimer disease. These observations are based upon analysis from autopsy brain tissue or more seldom from neurosurgical biopsies. The drawback of information from autopsy material is that the receptor changes represent the final stage of the dementia disorder. It might therefore be somewhat misleading to base therapeutic strategies on these findings. Hopefully, new imaging techniques such as positron emission tomography (PET) and single photon emission tomography (SPECT) will provide valuable new in vivo data from the earlier course of the disease. Among the transmitter systems changed in Alzheimer disease, the cholinergic system shows the most consistent deficits. Cholinergic muscarinic receptors seem to be preserved in Alzheimer brains while nicotinic receptors show losses. The number of serotonin (both 5-HT1 and 5-HT2) and glutamate receptors are also reduced. Interestingly, kainate receptors increase in number while NMDA receptors are reduced in cortical Alzheimer tissue. Common for all receptor changes in Alzheimer disease is that the changes in number of binding sites are seen while the affinity constant remains unchanged. alpha- and beta-receptors and dopamine receptors are relatively preserved in Alzheimer brains. Among the neuropeptides, losses in receptor sites have been reported for somatostatin and neuropeptide Y (NPY). Interestingly, the number of CRF receptors are increased in cortical areas of Alzheimer brains. Thus, the muscarinic (M1), kainate, and CRF receptors show receptor compensatory reactions probably due to degenerative reactions in Alzheimer disease. Few attempts have been made to visualize neuroreceptors in vivo in Alzheimer patients. The field, however, is in dynamic progress. Reduced numbers of nicotinic receptors have been visualized in the brain of Alzheimer patients by PET and [11C]-nicotine and confirm earlier observations in post-mortem brain tissues. A lower uptake of (R)(+)[11C]nicotine compared to (S)(-)[11C]nicotine in patients with a mild form of dementia might be a possible diagnostic marker. SPECT studies indicate preserved muscarinic receptors in Alzheimer brains. Analysis of neuroreceptor changes in peripheral nonneural tissues have shown a reduction in nicotinic and muscarinic receptors in peripheral lymphocytes obtained from Alzheimer patients.
 ...
PMID:Neuroreceptor changes in Alzheimer disease. 148 17

An implanted stimulating device chronically stimulated the left cervical vagus nerve in epileptic patients. Cerebrospinal fluid concentrations of free and total gamma-aminobutyric acid, homovanillic acid, 5-hydroxyindoleacetic acid, aspartate, glutamate, asparagine, serine, glutamine, glycine, phosphoethanolamine, taurine, alanine, tyrosine, ethanolamine, valine, phenylalanine, isoleucine, vasoactive intestinal peptide, beta-endorphin, and somatostatin were measured before and after 2 months of chronic stimulation in six patients. Significant increases were seen in homovanillic acid and 5-hydroxyindoleacetic acid in three patients, and significant decreases in aspartate were seen in five patients. These changes were associated with a decrease in seizure frequency.
 ...
PMID:Neurochemical effects of vagus nerve stimulation in humans. 150 37

Glutamate and several neuropeptides are synthesized and released by subpopulations of primary afferent neurons. These sensory neurons play a role in regulating the inflammatory and immune responses in peripheral tissues. We have explored what changes occur in the location and concentration of receptor binding sites for sensory neurotransmitters in two human inflammatory diseases, ulcerative colitis and Crohn's disease, using quantitative receptor autoradiography. The sensory neurotransmitter receptors included bombesin, calcitonin gene-related peptide-alpha, cholecystokinin, galanin, glutamate, somatostatin, neurokinin A (substance K), substance P, and vasoactive intestinal polypeptide. Of the nine receptor binding sites examined only binding sites for substance P and vasoactive intestinal peptide were significantly altered in the inflamed tissue. These data suggest that substance P is involved in regulating the inflammatory and immune responses in human inflammatory diseases and indicate a specificity of efferent action for each sensory neurotransmitter in peripheral tissues.
 ...
PMID:Alterations in receptors for sensory neuropeptides in human inflammatory bowel disease. 165 49

Neuronal degeneration that occurs in both ischemia and degenerative neurologic illnesses may involve excitotoxic mechanisms. In the present study, we examined whether cortical lesions with agonists acting at subtypes of glutamate receptors result in selective patterns of neuronal death. Injections of quinolinic acid, NMDA, homocysteic acid, kainic acid (KA), and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) were made at 2 sites in the dorsolateral frontoparietal cortex in rats. After 1 week, the cerebral cortex was either dissected for neurochemical studies, or animals were perfused for histologic evaluation. Concentrations of somatostatin (SS), neuropeptide Y (NPY), substance P (SP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay, while amino acids and catecholamines were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. NMDA agonists (quinolinic acid, homocysteic acid, and NMDA itself) resulted in dose-dependent reductions in glutamate and GABA, while SS, NPY, SP, CCK, and VIP were either unchanged or significantly increased in concentration. KA and AMPA at doses that resulted in comparable GABA depletions caused significant reductions in SS concentrations. Markers of cortical afferents were spared. All excitotoxins resulted in dose-dependent marked increases in uric acid concentrations. Histologic examination verified that lesions with NMDA agonists produced relative sparing of NADPH-diaphorase, SS, VIP, and CCK neurons. These results show that NMDA excitotoxin lesions result in a pattern of selective neuronal damage in the cerebral cortex that is similar to that which occurs in both ischemia and Huntington's disease.
 ...
PMID:Neurochemical characterization of excitotoxin lesions in the cerebral cortex. 167 Jul 82

Striatal atrophy in Huntington's disease (HD) is characterized by selective preservation of a subclass of neurons colocalizing NADPH-diaphorase (NADPH-d), somatostatin (SS), and neuropeptide Y (NPY), which have been reported to show three- to fivefold increases in SS-like immunoreactivity (SSLI) and NPY content. Since HD brain is capable of producing excessive quantities of the excitotoxin quinolinic acid (Quin), an N-methyl-D-aspartate (NMDA) receptor agonist, and since experimental Quin lesions show neuronal loss with sparing of NADPH-d/SS/NPY neurons, it has been suggested that Quin may be important in the pathogenesis of HD. In the present study we determined whether Quin stimulates SS gene function in cultured cortical cells known to be rich in NADPH-d/SS/NPY neurons. Cultures of dispersed fetal rat cortical cells were exposed to Quin (1 and 10 mM) with or without (-)-2-amino-5-phosphonovaleric acid (APV; 0.5 mM), an NMDA receptor antagonist, NMDA (0.2 and 0.5 mM), and glutamate (Glu; 0.5 mM). Medium and cellular SSLI was determined by radioimmunoassay and SS mRNA by Northern analysis with a cRNA probe. Quin induced significant (p less than 0.01) 1.6- and 2.5-4 fold increases in SSLI and SS mRNA accumulation, respectively, which were abolished by APV. Release of SSLI into the culture medium was stimulated two- to fivefold by Quin over a 2- to 20-h period. The increase in SS mRNA produced by Quin was time and dose dependent. A similar dose-dependent increase in SS mRNA comparable with that observed with Quin was induced by NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Quinolinic acid stimulates somatostatin gene expression in cultured rat cortical neurons. 167 45

The interaction between somatostatin and acetylcholine, two putative transmitters in the nucleus ambiguus, was investigated on single ambigual neurons in a brainstem slice preparation. Somatostatin reversibly inhibited the nicotinic cholinoceptor-mediated depolarization and inward current induced by acetylcholine. This inhibition persisted in the presence of tetrodotoxin (TTX) or Mn2+. In contrast, somatostatin enhanced both the glutamate-evoked depolarization and spiking discharges generated by current injection. These results suggest that somatostatin exerts a differential action in modulating excitatory inputs to the nucleus ambiguus at the level of postsynaptic receptors.
 ...
PMID:Somatostatin inhibits nicotinic cholinoceptor mediated-excitation in rat ambigual motoneurons in vitro. 167 25

Pharmacologic investigations into the transmission processes underlying fictive swallowing in the rat have disclosed the potential diversity of chemical signals used in central deglutitive pathways. Monoaminergic mechanisms appear to serve as links between subcortical structures and the medullary pattern generator of swallowing (PGS), and may play a critical role in maintaining internal facilitatory drive, required by the PGS for optimal responsivity to peripheral sensory input. Cholinergic bulbar interneurons form an integral component of the PGS subnetwork controlling esophageal peristalsis. Local GABA neurons exert a tonic inhibition of the buccopharyngeal stage, may regulate buccopharyngeal-esophageal coupling, and may contribute to peristaltic rhythmic generation at both the premotoneuronal and motoneuronal level. Receptor subtypes for excitatory amino acids (glutamate, aspartate) are differentially associated with deglutitive premotoneurons for both the buccopharyngeal and esophageal stage, as well as with ambiguus motoneurons. Preliminary evidence suggests the existence of excitatory peptidergic mechanisms involving thyrotropin-releasing hormone, vasopressin, oxytocin, and somatostatin, a probable candidate for excitatory transmitter in the solitarioambigual internuncial projection to motoneurons innervating esophageal striated musculature. Further validation of this experimental model may ultimately help to establish a framework for the clinical recognition, management, and exploitation of drug actions on central deglutitive neuroeffectors.
 ...
PMID:Neuropharmacologic correlates of deglutition: lessons from fictive swallowing. 168 Jun 8


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