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)

The possible heterogeneity of extrahypothalamic somatostatin receptors was studied in rat brain by quantitative radioautography. The respective distribution and relative proportion of two somatostatin receptor sub-types (SS1 and SS2) were assessed by using two radioligands, the non-selective probe [125I]Tyr3-D-Trp8-somatostatin14 and the SS1 selective analogue [125I]Tyr3-SMS 201-995. For both ligands, adjacent brain sections were processed in the presence of micromolar concentrations of either a non-discriminative competitor (somatostatin14) or SS1-selective analogue (SMS 201-995). The comparative analysis of the specific binding remaining in the presence of each non-radioactive competitor permitted a semi-quantitative analysis of the proportion of SS1 and SS2 receptor sub-types in each brain region examined. Data obtained correlate well with homogenate binding results reported previously [Reubi J. C. (1984) Neurosci. Lett. 49, 259-263]. Although the distribution patterns obtained with both radioligands were similar, [125I]Tyr3-SMS 201-995 labelled only a fraction of [125I]Tyr0-D-Trp8-somatostatin14-labelled sites in certain brain regions. For example, both superficial and deep cortical laminae, as well as the basolateral amygdaloid nucleus and CA1 hippocampal area exhibited different binding densities with [125I]Tyr0-D-Trp8-somatostatin14 depending on the competitor used in the assay (somatostatin14 or SMS 201-995). On the other hand, [125I]Tyr3-SMS 201-995 binding was eliminated in an identical fashion by either competitor in these very same brain areas. This suggests the existence of SS1 and SS2 somatostatin receptor sub-types in these regions. In all other brain areas examined, somatostatin receptor sites are apparently of the SS1 sub-type. The heterogeneity of somatostatin receptors observed in certain regions may have relevance for the various biological effects induced by somatostatin in the central nervous system.
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PMID:Quantitative radioautographic study of somatostatin receptors heterogeneity in the rat extrahypothalamic brain. 198 63

The relationship between neuronal calcium binding protein content (calbindin D28K: CaBP and parvalbumin: PV) and vulnerability to ischemia was studied in different regions of the rat brain using the four vessel occlusion model of complete forebrain ischemia. The areas studied, i.e. the hippocampal formation, neocortex, neostriatum and reticular thalamic nucleus (RTN), show a characteristic pattern of CaBP and PV distribution, and are involved in ischemic damage to different degrees. In the hippocampal formation CaBP is present in dentate granule cells and in a subpopulation of the CA1 pyramidal cells, the latter being the most and the former the least vulnerable to ischemia. Non-pyramidal cells containing CaBP in these regions survive ischemia, whereas PV-containing non-pyramidal cells in the CA1 region are occasionally lost. Hilar somatostatin-containing cells and CA3 pyramidal cells contain neither PV nor CaBP. Nevertheless, the latter are resistant to ischemia and the former is the first population of cells that undergoes degeneration. Supragranular pyramidal neurons containing CaBP are the most vulnerable cell group in the sensory neocortex. In the RTN the degenerating neurons contain both PV and CaBP. In the neostriatum, ischemic damage involves both CaBP-positive and negative medium spiny neurons, although the degeneration always starts in the dorsolateral neostriatum containing relatively few CaBP-positive cells. The giant cholinergic interneurons of the striatum contain neither CaBP nor PV, and they are the most resistant cell type in this area. These examples suggest the lack of a consistent and systematic relationship between neuronal CaBP or PV content and ischemic vulnerability. It appears that some populations of cells containing CaBP or PV are more predisposed to ischemic cell death than neurons lacking these proteins. These neurons may express high levels of calcium binding proteins because their normal activity may involve a high rate of calcium uptake and/or intraneuronal release.
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PMID:Relationship of neuronal vulnerability and calcium binding protein immunoreactivity in ischemia. 207 50

The hippocampal pyramidal cells provide an example of how multiple potassium (K) currents co-exist and function in central mammalian neurones. The data come from CA1 and CA3 neurones in hippocampal slices, cell cultures and acutely dissociated cells from rats and guinea-pigs. Six voltage- or calcium(Ca)-dependent K currents have so far been described in CA1 pyramidal cells in slices. Four of them (IA, ID, IK, IM) are activated by depolarization alone; the two others (IC, IAHP) are activated by voltage-dependent influx of Ca ions (IC may be both Ca- and voltage-gated). In addition, a transient Ca-dependent K current (ICT) has been described in certain preparations, but it is not yet clear whether it is distinct from IC and IA. (1) IA activates fast (within 10 ms) and inactivates rapidly (time constant typically 15-50 ms) at potentials positive to -60 mV; it probably contributes to early spike-repolarization, it can delay the first spike for about 0.1 s, and may regulate repetitive firing. (2) ID activates within about 20 ms but inactivates slowly (seconds) below the spike threshold (-90 to -60 mV), causing a long delay (0.5-5 s) in the onset of firing. Due to its slow recovery from inactivation (seconds), separate depolarizing inputs can be "integrated". ID probably also participates in spike repolarization. (3) IK activates slowly (time constant, tau, 20-60 ms) in response to depolarizations positive to -40 mV and inactivates (tau about 5s) at -80 to -40 mV; it probably participates in spike repolarization. (4) IM activates slowly (tau about 50 ms) positive to -60 mV and does not inactivate; it tends to attenuate excitatory inputs, it reduces the firing rate during maintained depolarization (adaptation) and contributes to the medium after-hyperpolarization (mAHP); IM is suppressed by acetylcholine (via muscarinic receptors), but may be enhanced by somatostatin. (5) IC is activated by influx of Ca ions during the action potential and is thought to cause the final spike repolarization and the fast AHP (although ICT may be involved). Like IM, it also contributes to the medium AHP and early adaptation. It differs from IAHP by being sensitive to tetraethylammonium (TEA, 1 mM), but insensitive to noradrenaline and muscarine. Large-conductance (BK; about 200 pS) Ca-activated K channels, which may mediate IC, have been recorded. (6) IAHP is slowly activated by Ca-influx during action potentials, causing spike-frequency adaptation and the slow AHP. Thus, IAHP exerts a strong negative feedback control of discharge activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Potassium currents in hippocampal pyramidal cells. 220 97

Hippocampal CA3 neurons from fetal rats were grafted to excitotoxic lesions in the CA3 subfield of the adult rat hippocampus and the formation of graft-host brain nerve connections examined. The excitotoxic lesions were induced by localized, stereotaxic injection of ibotenic acid (IA), a glutamic acid agonist, into CA3 of the dorsal hippocampus. The result was a so-called axon-sparing lesion with localized degeneration of nerve cells, but preservation of the extrinsic afferent fibers, now deprived of their targets. One week after the lesion a suspension of embryonic (E18-20) CA3 cells was grafted to the lesion site. Six weeks or more later the recipient brains were processed and analyzed by ordinary cell stains, histochemistry for acetylcholinesterase (AChE) and heavy metals (Timm staining), immunohistochemistry for the neuropeptides cholecystokinin and somatostatin and glial fibrillary acidic protein (GFAP) for astroglia, electron microscopy, and axonal tracing with retrogradely axonal transported fluorescent dyes or lesion-induced, anterograde degeneration combined with silver staining or electron microscopy. More than 90% of the grafts survived. They contained the normal types of CA3 neurons, which are mainly pyramidal cells, in addition to some normal, peptidergic, cholecystokinin- and somatostatin-reactive neurons. The grafts were innervated by AChE-positive, host cholinergic fibers, Timm-positive mossy fiber terminals from the host fascia dentata, and host commissural fibers traced by axonal degeneration. Efferent transplant projections were traced to the ipsilateral host CA1 (Schaffer collaterals) and the contralateral host hippocampus by retrograde axonal transport of fluorochromes injected into these host brain areas. All grafts analyzed by electron microscopy contained axonal varicosities resembling axonal growth cones even after long survival times. The results demonstrate that fetal rat hippocampal neurons, grafted to excitotoxic, axon-sparing lesions in the adult brain, can become both structurally and connectively well incorporated in the mature host central nervous system.
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PMID:Grafting of fetal CA3 neurons to excitotoxic, axon-sparing lesions of the hippocampal CA3 area in adult rats. 239 68

Acetylcholinesterase (AChE)-positive neurons were counted in the different layers of the rostral (septal) third, the middle third and the caudal (temporal) third of the hippocampus from 3 month (young) and 27 month old rats (aged) using AChE stained cryostat sections. The rats were treated with 3 and 2.5 mg of diisopropylphosphofluoridate/kg body weight, respectively 3 h before sacrifice. The study showed -1) a high numerical density of AChE-positive neurons (10.9 to 18.9 perikarya/mm2) in the hilus (fascia dentata), the str. oriens/pyramidale of CA1 and the subiculum, a particularly low density (less than 0.1 perikarya/mm2) in the str. granulosum and moleculare of the dentate area; -2) a significant (p less than 0.05) linear increase of the numerical density in most of the hippocampal layers from the rostral to the caudal pole; -3) no significant differences between young and aged animals; - and 4) a higher sensitivity to DFP-treatment in aged than in young animals. The distribution of AChE-positive neurons corresponds with the distribution of somatostatin-immunoreactive neurons described in the literature. A modulatory effect on neurotransmission is discussed as a possible function of the AChE in peptidergic neurons.
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PMID:Quantitative distribution of AChE-positive neurons in the hippocampus of young and aged rats. 239 23

1. In the kainic acid lesioned hippocampus there is a loss of functional inhibition that is associated with reduction of the IPSPs recorded intracellularly from the surviving CA1 pyramidal cells. The possible pre- or postsynaptic origin of this change has been investigated. 2. Iontophoretic application of GABA to the soma and dendrites of CA1 pyramidal cells indicated that there had been no change in the efficacy of the postsynaptic GABA receptors on these cells. 3. Although a pre-synaptic mechanism is implicated, at one week post lesion we were unable to find any difference in the Ca+ dependent K+ evoked release of endogenous GABA. However, at survival times greater than 1 week immunohistological studies showed a decrease in the number of somatostatin positive non-pyramidal cells in the stratum oriens of the CA1 area. 4. In addition to the reduction of functional inhibition, changes in excitatory neurotransmitter mechanisms were also found to contribute to the epileptiform burst discharge. A slow component of the epileptiform EPSP recorded from CA1 pyramidal cells has been recorded and was found to be antagonized by the NMDA-receptor antagonist D-APV. 5. Methods of controlling epileptiform activity in the kainic acid lesioned hippocampus have been tested. Stimulation of the substantia nigra and ventral tegmental areas produced profound inhibition of pyramidal cell activity in control hippocampi; however, they, were found to be ineffective in controlling the epileptiform burst. 6. A second method involved the use of hippocampal suspension grafts. Whilst this approach has yielded some encouraging data, further studies are necessary before the mechanism of the improvement in inhibitory synaptic function can be explained.
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PMID:Function of synapses in the CA1 region of the hippocampus: their contribution to the generation or control of epileptiform activity. 256 24

In area CA1 of hippocampus, a subpopulation of gamma-aminobutyric acid (GABA)-containing interneurons that make synaptic contacts on pyramidal cells also contains the neuropeptide, somatostatin. The effects of GABA and somatostatin on hippocampal pyramidal cells have been investigated separately, but it is not known whether an interaction occurs between these co-localized substances. We demonstrate that somatostatin has a potent inhibitory effect on GABA-mediated synaptic potentials which hyperpolarize pyramidal cells. This effect may be relevant to the well-documented epileptogenicity of the hippocampus, as well as the phenomenon of long-term potentiation, which is a well-studied example of synaptic plasticity.
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PMID:Selective depression of GABA-mediated IPSPs by somatostatin in area CA1 of rabbit hippocampal slices. 256 13

In the present work, we have characterized by film radioautography the effects of divalent cations and guanine nucleotide on specific receptor for somatostatin (SRIF) using 125I-TyrO-DTrp8-SRIF14 (125I-ToD8-SRIF) as a ligand. The experiments were performed on coronal 20-microM-thick sections cut at the level of the amygdala, thus allowing to study binding sites in several regions enriched in binding sites (frontal cortex, hippocampus CA1 and dentate gyrus, habenula, basolateral nucleus of the amygdala). In a preliminary set of experiments using brain cortical membranes it was found that 3 mM Mg2+ ions doubled the specific binding of 125I-ToD8-SRIF. However, Mg2+ enhanced equally by a factor of 3 affinities of high- and low-affinity binding sites as evidenced by SMS 201.995 displacement curves without modifying the ratio between high and low affinity sites. In radioautographic studies while SRIF14 and SRIF28 elicited monophasic displacement curves, SMS 201.995 displaced 125I-ToD8-SRIF binding in a biphasic manner in all regions tested but the baso-lateral nucleus of the amygdala. Radioautographic distribution of 125I-ToD8-SRIF binding sites was identical whether the sections were incubated with MgCl2 or with MnCl2 and almost undetectable in the absence of ions. In all structures investigated increasing concentrations of GTP totally inhibited 125I-ToD8-SRIF binding with an IC50 value of 3 microM. In conclusion, our results demonstrate that 125I-ToD8-SRIF-binding sites in brain occur on two different affinity states as assessed by a displacement curve using endogenous ligands and SMS 201.995. According to the comparable effects of divalent cations and GTP, the two subtypes of 125I-ToD8-SRIF-binding sites discriminated by SMS 201.995 are likely to correspond to interconvertible forms of the same receptor coupled to a G protein-transducing system.
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PMID:Regional distribution of somatostatin receptor affinity states in rat brain: effects of divalent cations and GTP. 257 46

The purpose of this study was to examine the structural and connective integration of developing hippocampal neurons grafted to ischemic lesions of the adult rat hippocampus. The 4-vessel occlusion model was used to cause transient cerebral ischemia which damages CA1 pyramidal cells in the dorsal hippocampus, but spares nonpyramidal neurons and afferents in the area. One week later, cell suspensions were made from the CA1 region of fetal (E18-20) rats and injected stereotaxically into the lesion. The recipient brains were examined 6 weeks to 6 months later for survival, morphology, and intrinsic and extrinsic connections of the grafts. The methods used included cell stains, histochemical staining for acetylcholinesterase (AChE), immunocytochemical staining for neuropeptides (cholecystokinin (CCK), somatostatin (SS), enkephalin (Enk) and an astrocytic marker, glial fibrillary acidic protein (GFAP), as well as tracing by retrograde axonal transport of fluorochromes and light and electron microscopy of anterograde axonal degeneration. The grafts survived well (80%) and were often quite large. They were well integrated in the lesioned host brain area, contained both pyramidal cells and neuropeptidergic neurons and displayed a near normal GFAP immunoreactivity for astrocytes. The latter contrasted the dense gliosis of the host ischemic lesion. Judged by the AChE staining the grafts were innervated by cholinergic host septohippocampal fibers. Ingrowth of host hippocampal commissural fibers was demonstrated by Fink-Heimer staining for degenerating nerve terminals following acute lesions of the hippocampal commissures. At the ultrastructural level degenerating, electron dense terminals of host commissural origin were found even deep inside the graft neuropil in synaptic contact with mainly dendritic spines. A transplant efferent connection to the host brain was demonstrated by retrograde fluorochrome tracing and consisted of a homotypic projection to more posterior levels of the ipsilateral host CA1 and subiculum. Minor abnormal, efferent projections to the host dentate molecular layer were shown in Timm staining. We conclude that fetal CA1 neurons grafted to one week old ischemic lesions of the dorsal CA1 in adult rats become structurally well incorporated and can establish nerve connections with the host brain.
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PMID:Neural grafting to ischemic lesions of the adult rat hippocampus. 270 27

Using the iodinated luteinizing-hormone-releasing hormone analogue [D-Ala6, N alpha MeLeu7, Pro9 NEt]-luteinizing-hormone-releasing hormone as radioligand, specific binding sites have been visualized in the rat both in the pituitary and the hippocampal formation of the brain. In the hippocampus, the CA1, CA2 and particularly CA3 regions were heavily labelled. These hippocampal sites have a pharmacological specificity resembling that of luteinizing-hormone-releasing hormone receptors in pituitary homogenates and could therefore represent true luteinizing-hormone-releasing hormone receptors. The luteinizing-hormone-releasing hormone superagonist [D-Ala6, Pro9 NEt]-luteinizing-hormone-releasing hormone and the potent antagonist [D-pGlu1, D-Phe2, D-Trp3,6]-luteinizing-hormone-releasing hormone were highly potent in displacing the iodinated luteinizing-hormone-releasing hormone analogue. The weak agonist [Gln8]-luteinizing-hormone-releasing hormone, however, was at least two orders of magnitude less potent. Somatostatin was inactive. Hippocampal luteinizing-hormone-releasing hormone receptors were species-specific, being present in the rat but not in the mouse, guinea-pig, hamster, rabbit and human brains. In order to identify the cellular location of these hippocampal receptors, various lesions were performed. Electrolytic lesions of the septal afferents did not reveal any receptor density change. Colchicine as well as kainic acid injections did, however, reduce considerably the number of hippocampal receptors. Interestingly, in the electrolytically and kainic-acid-lesioned animals, the appearance of non-displaceable luteinizing-hormone-releasing hormone binding sites within a well-defined area corresponding to the lesioned, gliosis-rich area was observed. The present results suggest the presence of pharmacologically specific, species-dependent, luteinizing-hormone-releasing hormone receptors located, at least partly, on intrinsic hippocampal neurons, in particular granule and pyramidal cells.
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PMID:Specific luteinizing-hormone-releasing hormone receptor binding sites in hippocampus and pituitary: an autoradiographical study. 281 69


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