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 binding parameters and distribution of somatostatin receptors were determined in the rat brain using in vitro light microscopic autoradiography. The proteolysis resistant somatostatin analog (des-Ala1-, Gly2-desamino-Cys3Tyr11-dicarba3,14-somatostatin; CGP 23,996) radiolabeled with 125iodine proved to be suitable for the localization of somatostatin receptors. Slide mounted tissue sections showed that 125I-CGP 23,996 bound to the somatostatin receptor with a mean Kd value of 4.0 nM. The mean density of receptors (maximum binding) was determined to be 182 fmol/mg of protein. Both somatostatin and unlabeled CGP 23,996 displayed high-affinity binding for somatostatin receptors with IC50 values of 6 and 5 nM, respectively. The areas containing the highest densities of receptors are the basal amygdaloid nucleus, medial habenular nucleus, stratum oriens and radiatum of CA1 and CA2, and the subiculum. High receptor density can also be found in the deep layers of the cingulate cortex and in the deep layers of temporal cortex. Moderate densities occur in the caudate-putamen, the granule cell layer of the cerebellum, CA3 area of the hippocampus, the molecular layer of the dentate gyrus and in the substantia nigra. Brain areas with low specific binding include the molecular layer of the cerebellum and the corpus callosum, a white matter area.
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PMID:Light microscopic autoradiographic localization of somatostatin receptors in the rat brain. 286 34

Somatostatin receptor-binding sites have been visualized by autoradiography in the rat central nervous system and the pituitary using the [Tyr3] derivative of the stable octapeptide somatostatin analogue SMS 201-995, code named 204-090 (sequence in text), which has been shown to label specifically high-affinity somatostatin receptors in brain homogenates. Receptors are particularly concentrated in the deeper layers of the cerebral cortex and large areas of the limbic system are rich in somatostatin receptors, in particular the hippocampus (CA1, CA2, dentate gyrus), most amygdaloid nuclei, the medial habenula and the septum. Parts of the olfactory, visual and auditory, as well as visceral and somatic sensory systems are heavily labelled, in particular the anterior olfactory nucleus and tubercle, the superior and inferior colliculi, the nucleus of the solitary tract, the substantia gelatinosa of the spinal cord and the spinal trigeminal nucleus. It is of interest that the central grey and locus coeruleus are also substantially labelled with [125I]204-090. Striatum has moderate amounts of somatostatin receptors, distributed in a patchy and heterogeneous way. Cerebellum and substantia nigra are virtually devoid of somatostatin receptors. The described receptors are likely to represent the molecular target for a variety of pharmacological actions of somatostatin in the central nervous system and they emphasize the role played by somatostatin as a neuropeptide in this organ.
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PMID:Autoradiographic mapping of somatostatin receptors in the rat central nervous system and pituitary. 286 57

High affinity somatostatin receptors have been measured in postmortem brains from 18 neurologically asymptomatic patients (mean age: 67 years) using the stable somatostatin analog 125I-204-090, DPhe-Cys-Tyr-DTrp-Lys-Thr-Cys-Thr(ol), as radioligand. In homogenates from human frontal cortex, high affinity (Kd = 0.52 nM; Bmax = 557 fmol/mg protein) receptors with pharmacological specificity for somatostatin, [D-Trp8]somatostatin and somatostatin-28 were found. The CNS distribution of these receptors was studied by autoradiography. Somatostatin receptors were distributed in varying densities throughout the whole brain. High concentrations are found in all cortical layers, the deeper layers (V-VI) being usually more dense than the superficial layers (I-III). The limbic system is heavily labeled, in particular hippocampus (CA1, dentate gyrus), most of the nuclei of the amygdala, and the habenula. Also parts of the basal ganglia are very rich in somatostatin receptors: the nucleus caudatus as well as the nucleus accumbens are very dense, whereas the globus pallidus is virtually unlabeled. Interestingly, significant amounts of somatostatin receptors are found in the human cerebellum, which is devoid of endogenous somatostatin. Other discrete areas of the CNS are enriched with somatostatin receptors: locus coeruleus, tuberal nuclei of the hypothalamus, claustum, tuberculum olfactorium as well as spinal trigeminal nucleus and substantia gelatinosa of the spinal cord. The substantia innominata is poor in somatostatin receptors. In general there is a good correlation in the distribution of somatostatin receptors in the human and rat brain and there is a reasonable correlation with endogenous somatostatin levels in human brain tissue, particularly in the larger structures. The very high density and the specific localization of somatostatin receptors in strategic key points in the CNS such as cortex, basal ganglia, limbic system and substantia gelatinosa suggests an important role of somatostatin in cognitive, sensory and extrapyramidal motor functions. The significance of somatostatin receptors in the human cerebellum remains to be elucidated.
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PMID:Distribution of somatostatin receptors in the human brain: an autoradiographic study. 287 25

Somatostatin has been localized in several hypothalamic and extrahypothalamic brain regions where it may function as a classical neurotransmitter or as a modulator of neural activity. In the present study, somatostatin binding sites were studied by incubation of coronal sections of rat forebrain with 125I-Tyr1-somatostatin, Ultrofilm autoradiography, computerized microdensitometry and comparison with 125I standards. Highest concentrations of somatostatin binding sites (fmol/mg protein) were found in the claustrum (151), basolateral nucleus of the amygdala (90), deep layers of the cerebral cortex (61), lateral olfactory nuclei (58), CA1 and CA2 areas of hippocampus (57), medial and lateral septal nuclei (54), and the medial habenula (44). Scatchard analysis of individual forebrain areas with high densities of somatostatin binding sites was also performed. Regulation of brain somatostatin binding sites may be studied as one approach to examining the involvement of central somatostatin pathways in various physiological and behavioral states.
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PMID:Quantitative autoradiographic analysis of somatostatin binding sites in discrete areas of rat forebrain. 288 15

The electrophysiological actions of somatostatin (somatotropin release inhibiting factor; SRIF) were investigated in the in vitro hippocampal slice preparation. Intracellular recordings were obtained from pyramidal neurons in area CA1 in slices of hippocampus from guinea pigs and rabbits. Somatostatin, applied via micropressure ejection to CA1 pyramidal-cell somata, was primarily excitatory. The effects, however, were quite variable, with nearly all cells displaying pronounced tachyphylaxis. A majority of cells was depolarized by SRIF, but hyperpolarizations or biphasic depolarization/hyperpolarization responses were also recorded. Only minimal conductance changes were associated with the SRIF-induced voltage changes. Depletion of SRIF, by injection of the intact animal with cysteamine several hours before preparing slices, resulted in no obvious abnormalities in hippocampal slice electrophysiology. Our results obtained with application of exogenous SRIF are consistent with the concept that SRIF acts as an excitatory neurotransmitter/neuromodulator in hippocampus. However, our attempts to demonstrate endogenous SRIF action have thus far been unsuccessful.
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PMID:Electrophysiological actions of somatostatin (SRIF) in hippocampus: an in vitro study. 288 22

The distribution of somatostatinlike immunoreactivity was studied in the hippocampal formation, retrohippocampal region, and temporal cortex in the human brain. Tissues from surgical biopsy and postmortem cases were used, and the immunogold/silver method on vibratome sections was introduced for routine applications in conjunction with primary antisera that recognise somatostatin-14 or somatostatin-28. Somatostatin-28 antisera readily stained numerous neurons, dendrites, and extensive axonal networks throughout the hippocampus and neighbouring cortex. Liquid phase absorption provided controls for specificity. The most prominent accumulations of somatostatin immunoreactive neurons and axons occurred in the hilus of the area dentata, in CA1, and in the entorhinal and perirhinal cortices. Axonal plexuses occurred throughout the hippocampal subfields but were particularly dense in those regions rich in somatostatin neurons. The distribution of somatostatin immunoreactive neurons and fibers parallels the distribution of neuropeptide Y (NPY) neurons and fibers in the hippocampus and cerebral cortex to a remarkable extent. Double labelling experiments with antisera against neuropeptide Y and somatostatin indicate a considerable frequency of coexistence of the two peptides in single neurons, particularly in large multipolar cortical neurons and also in the small bipolar white matter neurons. Regional variations exist in the amounts of coexistence found in the hippocampal subfields; somatostatin-NPY coexistence is particularly high in the hilus of the area dentata, the subicular complex, and the deep layers of the entorhinal and perirhinal cortices. In the hippocampi and temporal cortices in cases of Alzheimer-type dementia compared to those of age-matched control brains, there is a significant to severe loss of somatostatin immunoreactive neurons and axons. This loss is most severe in those regions with the highest indices of neurofibrillary tangles and neuritic plaques-the hilus of the area dentata, CA1, and the entorhinal and perirhinal cortices. Surviving somatostatin neurons are distorted with short dendrites and truncated axons. Neuritic plaques identified on double label experiments with thioflavin include somatostatin axons but not neurons.
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PMID:Somatostatin immunoreactive neurons in the human hippocampus and cortex shown by immunogold/silver intensification on vibratome sections: coexistence with neuropeptide Y neurons, and effects in Alzheimer-type dementia. 288 16

Immunocytochemical and electrophysiological evidence suggests that somatostatin may be a transmitter in the hippocampus. To characterize the ionic mechanisms underlying somatostatin effects, voltage-clamp and current-clamp studies on single CA1 pyramidal neurons in the hippocampal slice preparation were performed. Both somatostatin-28 and somatostatin-14 elicited a steady outward current and selectively augmented the noninactivating, voltage-dependent outward potassium current known as the M-current. Since the muscarinic cholinergic agonists carbachol and muscarine antagonized this current, these results suggest a reciprocal regulation of the M-current by somatostatin and acetylcholine.
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PMID:Somatostatin augments the M-current in hippocampal neurons. 289 68

The three major prosomatostatin-derived peptides found within CNS neurons are a 28-amino acid peptide (SS28), a cyclic 14 amino acid peptide (SS14) and a 12 amino acid peptide (SS1-12). Immunohistochemical studies demonstrate a differential distribution of these related forms of somatostatin within CNS neurons and have led to the suggestion that SS1-12 may represent the predominant neurotransmitter form of this family of peptides. Intracellular recordings from CA1 pyramidal neurons in the in vitro rat hippocampal slice revealed that application of SS14 and SS28 in nanomolar concentration produced neuronal hyperpolarization; synaptic responses, recorded extracellularly, were also reduced. In contrast, we were unable to demonstrate a pre- or postsynaptic action of SS1-12 on these neurons. These results do not support the hypothesis that SS1-12 functions as a central neurotransmitter in area CA1 of the hippocampus.
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PMID:Somatostatin(14) and -(28) but not somatostatin(1-12) hyperpolarize CA1 pyramidal neurons in vitro. 289 67

Experiments utilizing a combination of [3H]thymidine autoradiography and immunohistochemistry were conducted to determine the time of origin of somatostatin-immunoreactive (SSIR) neurons in the hippocampal formation of the rat. A quantitative and topographic description of neurogenesis in this peptide-containing neuronal system was generated using a computer-aided system to plot the position of labeled cells. Dissected and 'flattened' hippocampal preparations were used to facilitate the analysis of spatial gradients of SSIR cell development. The results indicate that most SSIR hippocampal cells are generated during a short embryonic period which extends from the 12th through the 15th day of gestation (E12-E15). Within this period of development, the distribution of SSIR cells follows a spatial gradient along the transverse or subiculo-dentate axis of the hippocampus. The earliest formed SSIR neurons, generated on E12 and E13, are preferentially distributed to the subiculum, those generated on E14 are most commonly observed throughout the CA1-CA3 fields of the hippocampus and SSIR neurons which become postmitotic on E15 are more heavily represented in the hilar region of the dentate gyrus than cells born at other stages of development. There was no clear-cut neurogenic gradient along the septotemporal axis of the hippocampus. These results indicate that somatostatin cells in the rat hippocampal formation are generated during the same prenatal period when glutamic acid decarboxylase (GAD)-positive neurons become postmitotic. These studies also suggest that quantitative developmental analyses of chemically specific cell types can reveal prominent features of cortical ontogeny that are not readily apparent in standard [3H]thymidine preparations.
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PMID:The time of origin of somatostatin-immunoreactive neurons in the rat hippocampal formation. 290 62

In the in vitro hippocampal slice somatostatin has been shown to cause a direct hyperpolarization of CA 1 pyramidal neurons by increasing a potassium conductance which is resistant to blockade by tetraethylammonium 4-aminopyridine, or cesium ions. Results reported here demonstrate that this somatostatin-induced hyperpolarization is blocked by 1 mM barium and 5 x 10(-5) M carbachol, with the action of carbachol being reversed by atropine. Barium and carbachol both inactivate the m-current and these results suggest that somatostatin may exert its hyperpolarizing action on CA1 pyramidal cells by activation of the m-current.
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PMID:Pharmacological evidence that somatostatin activates the m-current in hippocampal pyramidal neurons. 290 67


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