Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In situ hybridization histochemistry for somatostatin receptors-1, -2, -3 and -4 section and receptor autoradiography using [125I]CGP 23996, [125I]somatostatin-28, [125I]seglitide and [125I]Tyr3 octreotide were carried out to determine the expression of somatostatin receptor messenger RNAs and binding sites in the hippocampus and cerebral cortex of rats 21 days following generalized limbic seizures induced by subcutaneous injection of 12mg/kg kainic acid. In control rats, somatostatin-1 to somatostatin-4 receptor messenger RNAs were found in the pyramidal layer and granule cell layer of the dentate gyrus. After kainate treatment, the CA1 subfield displayed a selective decrease in somatostatin-3 and somatostatin-4 receptor hybridization signals of 35 and 41%, respectively, whereas no changes were observed in the remaining hippocampal areas. Somatostatin-1 and somatostatin-2 receptor messenger RNA expression in the hippocampus remained unaffected by kainate treatment. No effect of kainate was observed in the expression of somatostatin receptor messenger RNAs in the cerebral cortex. In control rats, the selective somatostatin-2 receptor ligands, [125I]seglitide and [125I]Tyr3 octreotide and the non-selective somatostatin receptor ligands [125I]CGP 23996 and [125I]somatostatin-28, labelled preferentially the stratum oriens and radiatum CA1, the granule and molecular layers of the dentate gyrus and the deep layers of the cerebral cortex. [125I]somatostatin-28 and [125I]CGP 23996 labelled sites were selectively decreased by 32 and 39%, respectively, in the stratum radiatum CA1 after kainate treatment. [125I]CGP 23996 binding was also decreased by 35% in the stratum oriens CA1 and by 36% on average in the stratum oriens and radiatum CA3. [125I]seglitide and [125I]Tyr3 octreotide binding was not affected by kainate in any hippocampal region. The granule and molecular layers of the hippocampus and the layers IV-VI of the cerebral cortex did not show changes in binding sites for any of the radioligands analysed. A 18 and 35% decrease in the spontaneous and 50 mM KCl-induced somatostatin release from hippocampal slices was found two days after kainate, a likely reflection of neuronal cell loss. No differences in somatostatin release were observed 21 days after kainate treatment. At this latter time, the rats had an enhanced susceptibility to tonic-clonic seizures induced by intraperitoneal injection of 30 mg/kg pentylenetetrazol, a subconvulsant dose in naive rats. Bilateral infusion of 6 micrograms RC 160, a selective somatostatin-2 receptor agonist, in the dentate gyrus 21 days after kainate, significantly reduced (P < 0.05) the number of animals with tonic-clonic seizures induced by pentylenetetrazol.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Functional effects of D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Trp-NH2 and differential changes in somatostatin receptor messenger RNAs, binding sites and somatostatin release in kainic acid-treated rats. 761 64

In situ hybridization histochemistry with somatostatin sst1-sst5 receptor messenger RNA-selective oligoprobes and quantitative receptor autoradiographic binding studies using [125I]Tyr3-octreotide, [Leu2,D-Trp22,125I-Tyr25]somatostatin-28 and [125I]CGP 23996 ([125I]c[Asn-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) were performed to determine the level of expression of somatostatin receptor messenger RNA and receptor binding sites in the hippocampal formation, limbic system and cerebral cortex of adult rats electrically kindled in the dorsal hippocampus. In control rats (implanted with electrodes but not electrically stimulated), the somatostatin-1 receptor-selective [125I]Tyr3-octreotide and the non-subtype-selective [Leu3,D-Trp22,125I-Tyr25]somatostatin-28 preferentially labelled the strata oriens and radiatum of the CA1 subfield of the hippocampus, the molecular layer of the dentate gyrus, the subiculum and presubiculum of the hippocampal formation, the inner layer of the frontal cortex, and the lateral and basolateral nuclei of the amygdala. The non-subtype-selective radioligand [125I]CGP 23996 (in 5 mM Mg2+ buffer) preferentially labelled the strata oriens and radiatum of the CA1 subfield of the hippocampus, the subiculum and the basolateral nucleus of the amygdala. Under conditions where primarily somatostatin-2 receptors were labelled, [125I]CGP 23996 (in 120 mM Na+ buffer) showed strong binding in the strata oriens and radiatum of the CA1 subfield of the hippocampus and the frontal cortex, whereas the dentate gyrus, subiculum and amygdala showed only weak signals. During and after kindling, no significant differences were observed between the ipsi- and contralateral sides of the hippocampus. A significant decrease (about 40%) of somatostatin receptor binding sites was observed in the molecular layer of the dentate gyrus with all radioligands (except [125I]CGP 23996 in Na+ buffer, which did not label this area) at stage 2 (pre-convulsive stage) and one week, but not one month, after stage 5 (generalized motor seizures). In contrast to somatostatin receptor binding, no alterations of the messenger RNA levels for sst1-sst5 receptors were found either at stage 2 or at stage 5. Similarly, no changes in receptor binding or messenger RNA levels were observed in the brain of rats which experienced a single afterdischarge. The present study shows a significant and selective decrease of somatostatin-1 receptor binding sites in the dentate gyrus of kindled rats. This is part of the plastic changes induced by kindling and may contribute to the increased sensitivity for the induction of generalized seizures during kindling.
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PMID:Status of somatostatin receptor messenger RNAs and binding sites in rat brain during kindling epileptogenesis. 895 79

We have investigated the role of somatostatin receptor subtypes sst2 and sst4 in limbic seizures and glutamate-mediated neurotransmission in mouse hippocampus. As compared to wild-type littermates, homozygous mice lacking sst2 receptors showed a 52% reduction in EEG ictal activity induced by intrahippocampal injection of 30 ng kainic acid (P < 0.05). The number of behavioural tonic-clonic seizures was reduced by 50% (P < 0.01) and the time to onset of seizures was doubled on average (P < 0.05). Seizure-associated neurodegeneration was found in the injected hippocampus (CA1, CA3 and hilar interneurons) and sporadically in the ipsilateral latero-dorsal thalamus. This occurred to a similar extent in wild-type and sst2 knock-out mice. Intrahippocampal injection of three selective sst2 receptor agonists in wild-type mice (Octreotide, BIM 23120 and L-779976, 1.5-6.0 nmol) did not affect kainate seizures while the same compounds significantly reduced seizures in rats. L-803087 (5 nmol), a selective sst4 receptor agonist, doubled seizure activity in wild-type mice on average. Interestingly, this effect was blocked by 3 nmol octreotide. It was determined, in both radioligand binding and cAMP accumulation, that octreotide had no direct agonist or antagonist action at mouse sst4 receptors expressed in CCl39 cells, up to micromolar concentrations. In hippocampal slices from wild-type mice, octreotide (2 micro m) did not modify AMPA-mediated synaptic responses while facilitation occurred with L-803087 (2 micro m). Similarly to what was observed in seizures, the effect of L-803087 was reduced by octreotide. In hippocampal slices from sst2 knock-out mice, both octreotide and L-803087 were ineffective on synaptic responses. Our findings show that, unlike in rats, sst2 receptors in mice do not mediate anticonvulsant effects. Moreover, stimulation of sst4 receptors in the hippocampus of wild-type mice induced excitatory effects which appeared to depend on the presence of sst2 subtypes, suggesting these receptors are functionally coupled.
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PMID:Somatostatin receptor subtypes 2 and 4 affect seizure susceptibility and hippocampal excitatory neurotransmission in mice. 1237 20

We investigated the distribution of somatostatin receptors (SSTs) in the hippocampi of SR (seizure-resistant) and SS (seizure-sensitive) gerbils in order to characterize the alterations in SST expressions induced by seizure activity. SST2A immunodensity in the hippocampus of SS gerbils was lower than that of SR gerbils, though its localization in the hippocampus was similar in both SR and SS gerbils. SST3 immunodensity in the hippocampus of SS gerbils was lower than in SR gerbils. In SR gerbils, strong SST4 immunoreactivity was detected in the dentate gyrus and in the CA3 region, in contrast little immunoreactivity was detected in these regions in SS gerbils. In SR and SS gerbils, the strong SST5 immunoreactivity in the hippocampus was also detected in the stratum oriens of the CA2-3 regions and the septal area of CA1 region. However, SST5 immunodensity in the stratum radiatum in SS gerbils was lower than in SR gerbils. These results are the first comprehensive description of the distribution of SSTs in the normal and epileptic hippocampus of gerbils, and suggest that these alterations in the hippocampus of the SS gerbil may be related with a regulatory mechanism for seizure activity in these seizure prone animals.
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PMID:The somatostatin receptors in the normal and epileptic hippocampus of the gerbil: subtype-specific localization and its alteration. 1296 33

The anti-convulsant properties of angiotensin IV (Ang IV), an inhibitor of insulin-regulated aminopeptidase (IRAP) and somatostatin-14, a substrate of IRAP, were evaluated in the acute pilocarpine rat seizure model. Simultaneously, the neurochemical changes in the hippocampus were monitored using in vivo microdialysis. Intracerebroventricularly (i.c.v.) administered Ang IV or somatostatin-14 caused a significant increase in the hippocampal extracellular dopamine and serotonin levels and protected rats against pilocarpine-induced seizures. These effects of Ang IV were both blocked by concomitant i.c.v. administration of the somatostatin receptor-2 antagonist cyanamid 154806. These results reveal a possible role for dopamine and serotonin in the anti-convulsant effect of Ang IV and somatostatin-14. Our study suggests that the ability of Ang IV to inhibit pilocarpine-induced convulsions is dependent on somatostatin receptor-2 activation, and is possibly mediated via the inhibition of IRAP resulting in an elevated concentration of somatostatin-14 in the brain.
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PMID:Involvement of the somatostatin-2 receptor in the anti-convulsant effect of angiotensin IV against pilocarpine-induced limbic seizures in rats. 1677 32

To identify whether altered expressions of voltage gated Ca(2+) channel (VGCC) are linked to inhibitory transmission abnormalities in the gerbil hippocampus, we investigated the effects of GABA receptor or somatostatin receptor (SST) antagonists/agonists on VGCC immunoreactivity in vivo. VGCC immunoreactivities in the hippocampus were significantly higher in seizure sensitive (SS) gerbils than in seizure resistant (SR) gerbils. P/Q-type VGCC immunoreactivity in the gerbil hippocampus was reduced by enhancement in GABA(A) and GABA(B) receptor-mediated transmission, but not by SST-mediated transmission. N-type VGCC immunoreactivity was reduced only by a SST agonist, whereas L-type (alpha1C) VGCC immunoreactivity was reduced only by a GABA(A) receptor agonist, and L-type (alpha1D) VGCC immunoreactivity was modulated by the GABA(B) receptor acting drugs. These findings provide a comprehensive description of the differential responses of VGCC subunits to alteration in GABAergic or somatostatinergic transmission. These findings also suggest that up-regulated VGCC immunoreactivity may be consequence of the neuronal excitability caused by a reduction in inhibitory neurotransmission in the gerbil hippocampus.
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PMID:The selective effects of somatostatin- and GABA-mediated transmissions on voltage gated Ca2+ channel immunoreactivity in the gerbil hippocampus. 1692 80

The neuropeptide somatostatin (SST) is highly expressed in brain regions associated with seizures. In hippocampus, SST expression and release is regulated by seizures, and SST-containing neurons within the hilus of the dentate gyrus are sensitive to seizure-induced death. In vivo and in vitro studies suggest that the loss of SST function in the dentate could contribute to epileptogenesis and seizure susceptibility. SST also has inhibitory actions in the CA1 and CA3 hippocampus indicating this peptide is an important homeostatic regulator throughout the hippocampus. In vivo studies show SST has robust antiepileptic properties with the major site of action being hippocampus. In rodents, somatostatin receptor subtype 2 (SST(2)) and SST(4) appear to mediate the majority of the antiepileptic actions of SST, with SST(2) predominate in rat and SST(4) in mouse. Thus SST receptors may be appropriate targets for new antiepileptic drugs (AEDs), although validation in human tissue is lacking.
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PMID:Somatostatin: an endogenous antiepileptic. 1822 32

Insulinomas are rare neuroendocrine tumors with an incidence of 4 per 1,000,000 person-years, being even rarer during pregnancy. During pregnancy most cases are recognized or become symptomatic during the first trimester. A 29-year-old woman, primigravida, was hospitalized in the 38th gestational week due to slurred speech, weakness and slow reaction patterns. An electroencephalogram and computed tomography scan of the brain and blood samples were normal. Blood pressure was 170-145/110-95 mmHg, albuminuria was moderate and there was moderate edema of the ankles. Labor started spontaneously the third day, 62 h after of hospitalization, and the patient gave birth to a healthy girl with no neonatal problems. Fourteen hours after delivery, the patient became comatose and developed universal clonic seizures. At the same time plasma glucose was <1.1 mmol/l and the patient responded immediately to intravenous glucose. The patient was managed with frequent small meals and continuous intravenous glucose. Postpartum testing was consistent with insulinoma and diazoxide treatment was initiated. Endoscopic ultrasound with biopsy showed an insulinoma in the head of the pancreas. During surgical exploration, four separate insulinomas were removed from the head of the pancreas. The hypoglycemic episodes resolved and the glucose levels normalized. Following biochemical diagnosis of insulinoma, diagnostic imaging procedures encountered include endoscopic ultrasonography, magnetic resonance imaging and digital subtraction angiography. Of isotopic procedures, somatostatin receptor scintigraphy (Octreoscan) and newer receptor binding ligands can be used in non-pregnant women. Intraoperative ultrasonography seems mandatory. The present case demonstrates that seizure disorders in non-diabetic pregnant women may be caused by hyperinsulinemia-induced hypoglycemia due to insulinoma.
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PMID:Insulinoma in a third-trimester pregnant woman combined with pre-eclampsia: a case report and review of the diagnostic strategies. 1864 15

Nesidioplastosis in adults is one of a rare causes of hyperinsulinemic hypoglycemia. Symptoms include chronic or recurrent hypoglycemias, often with neurological signs. Due to the looses of consciousness with coexisting seizures, in many cases patients are treated on epilepsy. Right diagnosis is usually late established, when the damages in the central nervous system (CNS) are irreversible. Early diagnosis of the disease and appropriate treatment might help to avoid serious disability in these patients. The aim of the study was to asses modern diagnostics of the nesidioblastosis with an emphasis on the biochemical and hormonal tests and imaging modalities. Patients enrolled to the study were aged between 18 and 72 years of age, and had chronic or recurrent hypoglycemia caused by hyperinsulinemia. In all patients fasting glucose and fasting insulinemia tests were performed, as well as the fasting blood test or in the 24-hour profile tests. Several techniques were used including ultrasound (US), abdominal computer tomography (CT), in two patients magnetic resonance imaging, scintigraphy of somatostatin receptors in seven patients, and in two patients scintigraphy with glucagone-like peptide-1 (GLP-1) analogue-labeled marker was done. In the performed tests low values of the blood glucose were found, whereas insulin levels, however not adequate to the blood glucose, were nearly always within the normal range. In the standard imaging only in one patient tumor lesion in the pancreatic tail was revealed, though not confirmed in the intraoperative histology. In the scintigraphy examination with the somatostatin analogue in one patient slightly increased collection of the marker in whole pancreas was reported and in the other patient focal collection in the pancreatic tail was observed. Scintigraphy with GLP-1 analogue revealed focal collection of the marker in one case. Five patients were underwent surgical treatment. In the histopathology in all operated patients hyperplasia of the endocrine pancreatic cells with positive immuno. histochemic reaction on the insulin was found. In the three cases despite hyperplasia of pancreatic islets, small sizes insulinomas were detected as well. 1. The diagnosis of nesidioblastosis should be taken into consideration in all patients with unclear-cause hypoglycemias, in whom simultaneously insulin blood level is inadequate to the level of glucose. 2. Widely available imaging examinations: US, CT, MRI are useless in the diagnosis of nesidioblastosis. 3. Among the imaging methods in preoperative diagnostics of hypoglycemia with concomitant hyperinsulinemia somatostatin receptor scintigraphy seems to have specific, though limited role - it is valuable only in the severe, diffused lesions. 4. Recurrent hypoglycemias after 70% excision of the pancreas may indicate the possibility of coexistence of pancreatic islets hyperplasia and insulin secreting insulinoma.
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PMID:[Symptoms and early diagnostic possibilities of pancreatic endocrine cells hyperplasia (nesidioblastosis)]. 2276 12

Cortistatin (CST)-14, a neuropeptide that is structurally and functionally related to somatostatin-14 (SRIF) binds all five somatostatin receptor subtypes (sst1-sst5). Using in vivo microdialysis and telemetry-based electroencephalographic recordings, we provide the first experimental evidence for anticonvulsive effects of CST-14 in a pilocarpine-induced seizure model in rats and mice and for the involvement of sst2 and sst3 receptors in these anticonvulsant actions of CST-14. Both receptor subtypes are required for the anticonvulsant effects of CST-14 given that co-perfusion of a selective sst2 antagonist (cyanamid15486) or a selective sst3 antagonist (SST3-ODN-8) reversed anticonvulsant effect of CST-14, and this, independently of each other. Next, as the ghrelin receptor has been proposed as a target for the biological effects of CST-14, we used ghrelin receptor knockout mice and their wild type littermates to study the involvement of this receptor in the anticonvulsive actions of CST-14. Our results show a significant decrease in seizure duration in both genotypes when CST-14 treated mice were compared with corresponding control animals receiving only pilocarpine. In addition, this CST-14-induced decrease was comparable in both genotypes. We here thus provide the first evidence that ghrelin receptors are not involved in mediating anticonvulsant actions of CST-14 in vivo.
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PMID:Cortistatin-14 mediates its anticonvulsant effects via sst2 and sst3 but not ghrelin receptors. 2468 42


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