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)

Several data obtained in the AF64A-model are of particular relevance for our understanding of the pathogenesis and progression of Alzheimer's disease. The AF64A-induced withdrawal of cholinergic function in the rat hippocampus was associated with reversible functional changes in other neurotransmitters, including noradrenaline, serotonin, somatostatin and glutamate, thereby mimicking changes in Alzheimer's disease. Identical changes in markers for synaptic vesicles were found in Alzheimer's disease and AF64A-model. A study on the role of gender revealed a higher susceptibility to the neurotoxic action of AF64A in female rats. The cholinergic deficit was also responsible for a disinhibition of the negative feedback regulation of glucocorticoids. Increased exposure to glucocorticoids, however, enhanced the vulnerability of hippocampal cholinergic neurons to AF64A. These data indicate that the AF64A-induced cholinergic deficit in the rat brain represents a reliable tool to study several mechanisms possibly involved in Alzheimer's disease.
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PMID:AF64A-induced brain damage and its relation to dementia. 789 96

The regional brain distribution of 125I-somatostatin (SRIH) binding sites was determined by quantitative radioautography in neonatally monosodium glutamate (MSG) treated adult male rats, a procedure which selectively destroys most neurons of the arcuate nucleus. Neonatal MSG treatment did not modify the extrahypothalamic distribution of 125I-SRIH-binding sites. In contrast, the number of 125I-SRIH-labeled cells in the ventrolateral part of the arcuate nucleus was strongly reduced in MSG-treated animals. The effect was selective for the anterior part of the arcuate nucleus and was not found in its posterior part or in the cells located more dorsally, beneath the ependymal zone of the periventricular nucleus. Intracerebroventricular SRIH injections, which increased growth hormone levels in control rats, were totally ineffective in MSG-treated animals. In contrast, the prolactin levels were equally stimulated by intracerebroventricular injections in control and MSG-treated animals. These results demonstrate that extrahypothalamic SRIH-binding sites are not located on neurons originating in the anterior arcuate nucleus neurons. In addition, 125I-SRIH-labeled cells in the ventrolateral part of the arcuate nucleus are necessary for the paradoxical stimulation of growth hormone secretion induced by intracerebroventricular SRIH injection, but do not seem to be essential for the increased prolactin secretion observed under these conditions.
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PMID:125I-somatostatin-labeled cells in the anterior arcuate nucleus mediate somatostatin effects on growth hormone but not prolactin secretion. 790 31

Short (90 min)-, mid (5 days)-, and long-term (15 days) ammonium acetate (5 mmol/kg IP) administration decreased the number of specific [125I][Tyr11]somatostatin receptors in synaptosomes from the frontoparietal cortex without changing the affinity constant. Administration of ammonium acetate did no affect the levels of somatostatin-like immunoreactivity in the frontoparietal cortex. The administration of a single dose of N-carbamyl-L-glutamate (1 mmol/kg) plus L-arginine (1 mmol/kg) 1 h before the last administration of ammonium acetate totally blocked the inhibitory effects of the latter on somatostatin receptor number in the frontoparietal cortex synaptosomes. 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 decreased target cell sensitivity to somatostatin, a phenomenon that could contribute to the depressed neuronal excitability induced by ammonia in the rat frontoparietal cortex.
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PMID:Effect of ammonium acetate on the somatostatinergic system in the rat frontoparietal cortex. 790 42

The presence of somatostatin in afferent fibers impinging on the goldfish Mauthner (M-) cell was determined using immunohistochemical methods, combined with confocal and electron microscopy, and the relationship of this peptide with inhibitory and excitatory terminals was studied. Somatostatin-reactive boutons were present only on the distal part of the M-cell's lateral dendrite. Somatostatin immunoreactivity was observed in typical large myelinated club endings (LMCEs) corresponding to mixed (electrical and chemical) eighth nerve primary afferent fibers. The axoplasm of these fibers contained dense-core vesicles (DCVs) dispersed among round vesicles. We have made a novel finding that the excitatory transmitter glutamate is present in LMCEs. Colocalization of this amino acid with somatostatin was detected in 75% of these endings using postembedding staining with gold particles of various sizes. The other structures labeled by somatostatin antibody were found to be small vesicle boutons (SVBs), which establish symmetrical synapses and contain a population of pleiomorphic vesicles with DCVs scattered among them. Double labeling with antibodies against glutamic acid decarboxylase and GABA allowed the definition of three types of biochemically characterized terminals: [somatostatin-GABA], [GABA], and [somatostatin]. However, the occurrence of DCVs in SVBs stained for GABA alone suggests that neuropeptides other than somatostatin may also coexist with GABA in this class of boutons. The coexistence of somatostatin with both inhibitory and excitatory neurotransmitters acting on the same region of a postsynaptic cell is discussed in relation to the role postulated for this peptide in synaptic plasticity.
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PMID:Colocalization of somatostatin with GABA or glutamate in distinct afferent terminals presynaptic to the Mauthner cell. 790 14

This review describes the neuropathology and pathophysiology of interneurons in dorsal hippocampus of the adult rat subjected to transient global cerebral ischemia. The object is to verify if the interneurons die or survive after an ischemic insult, and study if ischemia changes GABA inhibition in the period preceding delayed CA1 pyramidal cell death. The findings are discussed from the point of the hypothesis that loss of GABA inhibition may result in excitatory hyperactivity (possibly epilepsy) and excitotoxic glutamate release. Thereby, early ischemic damage to interneurons may exacerbate the ischemic process resulting in the major and delayed CA1 cell death in hippocampus. Interneurons, located in dentate hilus, and a small number of interneurons located in the mossy fiber layer are selectively lost after ischemia. These interneurons contain somatostatin and neuropeptide Y, but the inhibitory or excitatory nature of them is unknown. However, counts of all hippocampal cells immunoreactive for glutamic acid decarboxylase showed that the GABA interneurons survive ischemia. It is therefore suggested that the vulnerable interneurons in hilus and the mossy fiber layer do not contain GABA. As the GABA interneurons, other hippocampal interneurons also survive ischemia. Among these, the CA1 and CA3 interneurons containing neuropeptide Y demonstrate permanently reduced immunoreactivity for neuropeptide Y, evident 1-2 days after ischemia. Another subpopulation transiently shows a decrease in immunoreactivity for parvalbumin approximately 4 days after ischemia. These results are in contrast to the finding that protein synthesis in hippocampal interneurons returns to preischemic levels 9 hours after ischemia. The integrity between excitation and inhibition in CA1 is unchanged in hippocampal slices taken from animals 1-2 days after ischemia. Furthermore, GABA can readily be released upon potassium stimulation in the period preceding CA1 pyramidal cell death. Binding to hippocampal benzodiazepine sites, however, declines prior to ischemic CA1 pyramidal cell death. It is demonstrated that administration of diazepam and GABA uptake inhibitors during this period offers postischemic neuron protection in CA1. There is no conclusive evidence of excitatory hyperactivity preceding ischemic CA1 pyramidal cell death. On the contrary, results from Chang et al. (1) suggest that ischemic loss of interneurons in the dentate hilus is associated with an increase in inhibition. However, it is suggested that GABA inhibition is insufficient to counterbalance the detrimental process during normal or even reduced postischemic excitation, since drugs believed to increase GABA inhibition reduce ischemic cell death. The early and permanent reduction in neuropeptide Y immunoreactivity may reflect a reduced capacity of these interneurons to release neuropeptide Y and thereby reduce presynaptic glutamate release.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interneurons in rat hippocampus after cerebral ischemia. Morphometric, functional, and therapeutic investigations. 790 56

The neuropharmacologic basis of infantile spasms and the mechanism by which adrenocorticotropic hormone (ACTH) exerts its therapeutic effects are unknown. This is a critical review of cerebrospinal fluid neurotransmitters or their metabolites in infantile spasms before and during treatment with ACTH, and of clinical drug trials with drugs acting on neurotransmission. Cerebrospinal fluid studies have shown lower gamma-aminobutyric acid (GABA), ACTH, and 5-hydroxyindoleacetic acid concentrations in patients with infantile spasms compared to controls, elevated lysine and glutamate, variable or no differences in homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, norepinephrine, corticotropin-releasing hormone, and beta-endorphin. Chronic treatment with ACTH in infantile spasms reduces cerebrospinal fluid GABA, beta-endorphin, and somatostatin, increases norepinephrine and tyrosine, and has variable or no effect on homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, histamine, and tryptophan. Small therapeutic trials with drugs that act through different neurotransmitters such as methysergide, alpha-methylparatyrosine, various benzodiazepine agonists, and vigabatrin lend some support to a role for GABA and monoamines in infantile spasms. These data, though promising, provide only a hint of potential neurotransmitter disturbances, and more basic and clinical data are needed.
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PMID:Putative neurotransmitter abnormalities in infantile spasms: cerebrospinal fluid neurochemistry and drug effects. 791 15

A small surgical lesion of the parietal cortex induces an increase in the expression of several messenger RNAs varying from 172 to 980% in the entire homolateral cerebral cortex, as detected by quantitative in situ hybridization histochemistry. The messenger RNAs encoding the immediate early genes of the leucine zipper family (c-fos, c-jun, jun-B), the Zinc finger family (zif268), the glucocorticoid receptor family (NGFI-B) and the interferon family (PC4) are increased within 2 h after the lesion and return to normal levels at 6 h. The messenger RNAs encoding cholecystokinin, neuropeptide Y, somatostatin and the synthetizing enzyme of the neurotransmitter GABA, glutamate decarboxylase, are elevated within one day and return to normal levels after six days. An intraperitoneal injection of the N-methyl-D-aspartate receptor antagonist dizocilpine maleate, 30 min before surgery, prevented either the induction of immediate early gene expression or the increase of neuropeptide and glutamate decarboxylase messenger RNA expression. This study demonstrates that a minimal cortical lesion induces extensive changes in gene expression and that the mechanism(s) leading to these changes involves the action of glutamate at the N-methyl-D-aspartate receptor. These modifications may be of importance in explaining diffuse changes not related to neuronal circuitry in several conditions.
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PMID:Homolateral cerebrocortical increase of immediate early gene and neurotransmitter messenger RNAs after minimal cortical lesion: blockade by N-methyl-D-aspartate antagonist. 791 80

As shown on cultured astrocytes from the mouse, in the presence of adenosine deaminase, 2-chloroadenosine by acting on A1-adenosine receptors potentiated the activation of phospholipase C induced by the alpha 1-adrenergic agonist, methoxamine. This potentiation required the presence of external calcium and was blocked by pertussis toxin. Moreover, this potentiation resulted from a cascade of events: activation (by calcium and protein kinase C) of a phospholipase A2 coupled to A1-adenosine receptors, release of arachidonic acid, which inhibited the reuptake of glutamate into astrocytes and finally additional activation of phospholipase C by externally accumulated glutamate through metabotropic receptors. The effects of 2-chloroadenosine and methoxamine were respectively mimicked by somatostatin and substance P while endothelins reproduced the combined effects of 2-chloroadenosine and methoxamine. Conditioned media from treated astrocytes enriched in glutamate stimulated phospholipase C in cultured striatal neurones. In addition, glutamate alone was also found to stimulate phospholipase A2 in astrocytes through receptors exhibiting a pharmacological profile distinct from metabotropic receptors coupled to phospholipase C and the glutamate response was potentiated by ATP. Moreover, the neuronal arachidonic acid production evoked by glutamate was potentiated by acetylcholine. Finally, the combined application of 2-chloroadenosine and methoxamine on striatal astrocytes reduced the permeability of gap junctions between astrocytes and this response was mimicked by arachidonic acid. Together, these results emphasized the contribution of astrocytes in the regulation of glutamatergic transmission.
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PMID:Glial receptors and their intervention in astrocyto-astrocytic and astrocyto-neuronal interactions. 792 48

We have mutated the aspartate residue in the putative second transmembrane spanning domain of the alpha 2A-adrenergic receptor (alpha 2AAR) to the non-negatively charged asparagine (D79N) and glutamine (D79Q) and the negatively charged glutamate (D79E) residue in an effort to better characterize the role of this residue, highly conserved among G-protein-coupled receptors, in Na+ regulation of ligand binding and in receptor G-protein coupling. Allosteric modulation of receptor-ligand interactions by Na+ is retained by the D79E alpha 2AAR but lost upon mutation to the uncharged D79N and D79Q residues. Loss of allosteric effects of Na+ is paralleled by a complete loss of retrograde information transfer from G-proteins to alpha 2AAR in AtT20 cells, measured via the sensitivity of radiolabeled agonist binding to Gpp(NH)p. In contrast to the complete elimination of retrograde signaling via the D79N and D79Q alpha 2AAR, anterograde information transfer from receptor to G-protein is modified in a more subtle quantitative way, since agonist-stimulated GTPase activity via D79N and D79Q alpha 2AAR, although apparently attenuated compared to wild type and D79E alpha 2AAR, is no less than the GTPase activity elicited by endogenous somatostatin receptors in AtT20 cells. These data indicate that a negative charge at amino acid residue 79 forecasts sensitivity to allosteric regulation by monovalent cations and its mutation to non-negatively charged residues elicits a nonparallel modulation of receptor-->G-protein versus G-protein-->receptor communication between alpha 2AAR and pertussis toxin-sensitive GTP-binding proteins.
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PMID:Mutation of an aspartate residue highly conserved among G-protein-coupled receptors results in nonreciprocal disruption of alpha 2-adrenergic receptor-G-protein interactions. A negative charge at amino acid residue 79 forecasts alpha 2A-adrenergic receptor sensitivity to allosteric modulation by monovalent cations and fully effective receptor/G-protein coupling. 796 41

Recent findings indicate that excitatory amino acids (EAAs) can modulate growth hormone (GH) secretion in several mammalian species in vivo and in vitro. In this study, we examined the effects of EAA receptor antagonists [N-methyl-D,L-aspartate (NMDA), kainic acid, L-glutamate] on GH secretion by the reverse hemolytic plaque assay (RHPA). Anterior pituitary cells of adult male Sprague-Dawley rats were enzymatically dispersed and subjected to RHPA. EAA receptor agonists increased the mean plaque area in a dose-dependent manner: the maximal increase was observed at 10 microM and increased the fraction of somatotrophs forming large plaques. NMDA (10 microM) did not increase the mean plaque area in the presence of the NMDA receptor antagonists 10 microM AP-7 and 10 microM MK-801. Coincubation of kainic acid with the non-NMDA receptor antagonist CNQX blocked the kainic-acid-stimulated increase in GH secretion. The addition of MK-801, AP-7 or CNQX to glutamate caused a partial reduction of the mean plaque area. Ten micromoles per liter glutamate with 10 nM GH-releasing hormone (GHRH) produced an additive effect on GHRH-induced GH release. Somatostatin suppressed the stimulatory action of glutamate. We speculate that glutamate plays a role in the regulation of GH secretion.
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PMID:Effect of excitatory amino acid receptor agonists on secretion of growth hormone as assessed by the reverse hemolytic plaque assay. 796 75


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