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)

We have previously shown that somatostatin (SS) immunoreactive (-i) neurons, located in the rat dentate hilus, are vulnerable to cerebral ischemia (Johansen et al., 1987). Within 40 h after ischemia, the cells show clear signs of cell death. At the same time, we observed that dying cells, located in the projection field of the mossy fibers (dentate hilus and CA3 mossy fiber layer), accumulate free zinc. We now demonstrate that the hilar cells, accumulating zinc after ischemia, are SS-i cells. Since it is known that hypothermia can ameliorate ischemic brain damage, we furthermore studied whether hypothermia (29 degrees C) protects the vulnerable SS-i neurons in hilus from zinc accumulation and ischemic cell death. We found that hypothermia both prevented ischemia-induced neuronal zinc accumulation and cell death. We speculate that hilar SS-i cells are highly vulnerable to ischemia, and develop rapid ischemic cell death, because they accumulate zinc shortly after ischemia.
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PMID:Hypothermia protects somatostatinergic neurons in rat dentate hilus from zinc accumulation and cell death after cerebral ischemia. 768 76

The distribution and extent of glutamate decarboxylase 65 (GAD65) mRNA-labeled neurons that coexpress pre-prosomatostatin mRNA were studied in the rat dentate gyrus of the dorsal and ventral hippocampal formation. The distribution of each group of neurons was determined initially by nonradioactive in situ hybridization experiments with digoxigenin-labeled riboprobes for GAD65 mRNA and pre-prosomatostatin mRNA. Double labeling experiments were then conducted with digoxigenin-labeled riboprobes for GAD65 mRNA and 35S-labeled riboprobes for pre-prosomatostatin mRNA. In the dorsal and ventral dentate gyrus, GAD65 mRNA-containing neurons were highly concentrated in the hilus and in the innermost part of the granule cell layer whereas only a few labeled neurons were scattered in the molecular layer. Pre-prosomatostatin mRNA-containing neurons were primarily located in the hilus and were virtually absent from the molecular and granule cell layers. The simultaneous detection of GAD65 and pre-prosomatostatin mRNAs in the same sections showed that the vast majority of pre-prosomatostatin mRNA-containing neurons in the hilus of the dentate gyrus were also labeled for GAD65 mRNA. In contrast many GAD65 mRNA-labeled neurons did not contain pre-prosomatostatin mRNA. These included all neurons in the molecular layer, neurons within the inner granule cell layer and neurons interspersed amongst double labeled neurons in the hilus. Quantitative analyses indicated that a very high percentage of hilar pre-prosomatostatin mRNA-containing neurons coexpressed GAD65 mRNA in the dorsal (96%) and ventral (92%) dentate gyrus. In contrast only a part of the total population of hilar GAD65 mRNA-containing neurons were also labeled for pre-prosomatostatin mRNA in the dorsal (43%) and ventral (53%) dentate gyrus. In the CA3c region, the percentages of neurons containing both mRNAs were similar to those observed in the hilus. The findings demonstrate that the vast majority of hilar somatostatin neurons, which have previously been shown to be extremely vulnerable to ischemia and seizure-induced damage, are GABA neurons. However, the total population of GAD65 mRNA-containing neurons in the hilus is substantially larger than the somatostatin-containing subgroup, and these findings reinforce the suggestion that GABA neurons are a major component of the diverse group of neurons in the hilus of the dentate gyrus.
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PMID:Somatostatin neurons are a subpopulation of GABA neurons in the rat dentate gyrus: evidence from colocalization of pre-prosomatostatin and glutamate decarboxylase messenger RNAs. 770 May 25

The influence of the somatostatin analogue angiopeptin on transplant arteriosclerosis was investigated using two aortic transplantation rat models. One was characterized by ischemia/reperfusion-induced changes in syngeneic transplants while immunologically induced changes dominated in the other allogeneic model. Angiopeptin, 100 micrograms/kg per day, was administered continuously until the sacrifice of the rats after 8 weeks. No additional immunosuppression was used in either model. An image analysis system was used to quantify the intimal and medial thicknesses of the grafts. In the syngeneic grafts, the intimal thickness was less than 50% of that of control grafts (P < 0.05), but no difference was seen in the allogeneic model. The expression of selected cells, TGF-beta s, and PDGF and PDGF alpha-receptors was detected immunohistochemically and displayed a similar picture in control and angiopeptin-treated grafts in both models. We conclude that angiopeptin has no clear immunosuppressive properties but may counteract ischemia-induced transplant arteriosclerosis.
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PMID:Effects of angiopeptin on transplant arteriosclerosis in the rat. 776 91

The influence of transient cerebral ischemia on the expression of somatostatin (SS) mRNA and peptide in hippocampal neurons was studied in the rat. Animals survived 10 min of 4-vessel occlusion ischemia during systemic hypotension for 1 h, 1 day, 2 days, 4 days, and 16 days, respectively. SS mRNA and peptide were detected with nonradioactive probes in brain sections by means of in situ hybridisation and immunocytochemistry. Then SS mRNA and peptide positive neurons in hippocampus were counted. The neuronal expression of the two markers correlated well in control and ischemic sections. In the dentate hilus, SS mRNA and peptide were lost permanently from day 2 after ischemia, in parallel with ischemic cell death and loss of the neurons. In CA1, where all interneurons containing SS survive an ischemic insult, we found a transient decrease of SS mRNA and peptide at 2-4 days after ischemia. The SS mRNA was most reduced. We conclude that ischemia transiently reduces levels of SS mRNA and peptide in surviving hippocampal interneurons. This process is brief and delayed in mild ischemia, and not expressed in vulnerable hilar neurons.
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PMID:Expression of somatostatin mRNA and peptide in rat hippocampus after cerebral ischemia. 790 82

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

Changes in glucose metabolism mediated by natural somatostatin and two derivatives (octreotide, 008) were studied in hypoxic ischemic cell injury of the isolated perfused rat liver. The tested somatostatin and its analogues were previously shown to exert protective actions in liver damage induced by hypoxic ischemia and reperfusion. In isolated perfused livers of rats starved for 24 hours and unstarved rats flow rate was reduced and oxygen supply interrupted for 180 min. Then the livers were normoxically reperfused for 30 min. Glucose and lactate concentration, as well as LDH and GLDH activity, were determined in the effluent. In starved and unstarved rat livers hypoxic ischemia resulted in a substantial enzyme release. In livers harvested from unstarved rats hepatic glucose release was noticed which ceased towards prolonged low flow ischemia. In livers harvested from starved rats containing low hepatic glycogen concentration only minimal hepatic glucose release was present. In starved and unstarved rats pretreatment with somatostatin, octreotide, and 008 significantly reduced LDH and GLDH release (p < 0.001). In unstarved rats natural somatostatin and octreotide pretreatment resulted in a substantial output of glucose during the hypoxic ischemic perfusion period (p < 0.001), whereas livers with 008 pretreatment did not show any difference in glucose release compared to controls. In livers harvested from starved rats neither somatostatin nor octreotide nor 008 pretreatment led to a difference in glucose output observed in controls. Natural somatostatin and octreotide cause a strong hepatic glucose release even under hypoxic ischemic conditions in rat livers with filled glycogen stores. The protective action of natural somatostatin, octreotide, and 008 is not mediated by changes in glucose metabolism, and is not related to endocrine activity.
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PMID:Rat liver injury induced by hypoxic ischemia and reperfusion: protective action by somatostatins is independent from changes in glucose metabolism. 792 89

The effects of a very short ischemic insult on hilar somatostatin (SS) neurons were investigated in the gerbil hippocampus by means of immunocytochemistry and in situ hybridization histochemistry. A selective and significant loss of 40% of hilar SS neurons took place after 1 day, and a 60% loss after 7 days following 2 min of ischemia, while no SS neurons were lost during recirculation after 1 min of ischemia. Repeated 2-min periods of ischemia, which induced ischemic tolerance by vulnerable CA1 neurons, caused almost complete loss of hilar SS neurons. This study clearly demonstrates that hilar SS neurons are more vulnerable to ischemic insult than CA1 pyramidal neurons. Ischemic tolerance may be induced during the progressive loss of SS neurons in the hilus by changes in their synaptic connections to CA1 pyramidal neurons.
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PMID:Hilar somatostatin neurons are more vulnerable to an ischemic insult than CA1 pyramidal neurons. 809 19

Natural somatostatin and two synthetic derivatives (octreotide, 008) were tested for their ability to prevent hypoxic ischemic cell injury of the isolated perfused rat liver. The cyclic octapeptide octreotide is known to have endocrine and cytoprotective activities, whereas the cyclic hexapeptide 008 exerts protective actions without any endocrine effects. In isolated perfused rat livers flow rate was reduced and oxygen supply interrupted for 180 min. Then the livers were normoxically reperfused for 30 min. LDH and GLDH activity as well as Ca2+ concentration was determined in the effluent. Hypoxic ischemia led to a substantial enzyme release from the liver and to a strong Ca2+ influx. Pretreatment with somatostatin, octreotide and 008 significantly reduced LDH and GLDH release (P < 0.001). The somatostatins significantly increased the Ca(2+)-influx into the hypoxic, ischemic perfused rat liver (P < 0.001). Ca(2+)-influx is known to be an essential factor in the final common pathway of cell death induced by hypoxic ischemia. Even though the administration of the somatostatins was associated with an enhanced Ca(2+)-influx, the somatostatins reduced hypoxic ischemic liver injury.
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PMID:Rat liver injury induced by hypoxic ischemia and reperfusion: protective action by somatostatin and two derivatives. 809 90

Pancreatic-derived proteases play a central role in the pathogenesis of ischemic intestinal injury. We postulated that exocrine blockade by pretreatment with a long-acting somatostatin analogue, octreotide acetate, would attenuate ischemic mucosal injury. Sprague-Dawley rats received subcutaneous octreotide (10 micrograms/kg/d) for 6 days by means of surgically implanted infusion ports. In a group of sham control rats, splanchnic blood flow (portal vein Doppler measurement) and duodenal trypsin activity (p-toluene sulfonyl-L-arginine methyl ester assay) were determined. In a separate experiment, pretreated animals were subjected to 60 minutes of superior mesenteric artery ischemia alone or followed by 30 minutes of reperfusion. Gross extent of hemorrhagic necrosis and microscopic injury (rank analysis) were assessed by a blinded observer. Pretreatment with octreotide reduced intraluminal duodenal trypsin activity by 46% without affecting portal blood flow. However, octreotide pretreatment significantly attenuated the microscopic depth of injury during ischemia and the extent of gross injury during reperfusion. It appears that somatostatin may have an adjuvant role in the prevention or progression of intestinal ischemic injury.
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PMID:Somatostatin attenuates ischemic intestinal injury. 809 72

The mechanism of delayed death of pyramidal cells in the hippocampal CA1 region and the acute death of various types of hilar neurons after ischemia is still unknown. Excitotoxicity may play a role in ischemic cell death, a prerequisite of which is the development of increased excitability or an enhanced excitatory transmission in the selectively vulnerable subfields of the hippocampus. Such changes may take place upon the loss or malfunction of local inhibitory neurons in the early postischemic period. In the present study we examined the vulnerability of non-pyramidal neurons containing a recently discovered calcium binding protein, calretinin, in the rat hippocampus following 15 min ischemia induced by four-vessel occlusion. Immunostaining for calretinin enabled us to visualize a new type of spiny non-pyramidal cell in the hippocampus specifically associated with the mossy fiber system. This cell type is present exclusively in regions where mossy fiber terminals occur, i.e. in the hilus of the dentate gyrus and in stratum lucidum of the CA3 subfield. A selective loss of immunoreactivity in these neurons was already observed at 12-24 h after ischemia, when the pyramidal cells in the CA1 region showed no signs of damage. At a survival time of two to three days, most if not all spiny calretinin-immunoreactive cells had disappeared from the hippocampus. Other types of calretinin-containing GABAergic neurons were also reduced in number, but only at a time when CA1 pyramidal cells also started to degenerate, i.e. two to three days after ischemia. We speculate that the early loss of spiny calretinin-containing cells, together with other non-pyramidal cells associated with the mossy fiber system (somatostatin-containing neurons and mossy cells of the hilus), may result in pathological network activity in the hippocampus, which may ultimately lead to an increased excitatory transmission and delayed pyramidal cell death in the CA1 region.
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PMID:Early degeneration of calretinin-containing neurons in the rat hippocampus after ischemia. 825 22


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