UNIPROT:P61278 - FACTA Search

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Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These studies explore the distribution of putative neuroactive peptides in the human olfactory bulb. Localization of synaptophysin-, serotonin-, cholecystokinin-, substance P-, and somatostatin-like staining was examined by immunocytochemical protocols. The results provide new insights into the composition and laminar segregation of subpopulations of neurons and neuronal processes in the human olfactory bulb. The prominent synaptophysin-like immunoreactivity observed in the glomeruli of the human olfactory bulb is consistent with the notion that the density of synapses, and hence the density of synaptic vesicles, is highest in the glomeruli. Serotonin-like immunoreactivity suggested a variable innervation of glomeruli ranging from a dense tangled ball of fibers within the glomerulus to a sparse innervation by a single immunoreactive fiber. There was no evidence of serotonin-like immunoreactive cell bodies in either the olfactory bulb proper, anterior olfactory nucleus, or proximal regions of the lateral olfactory tract. Cholecystokinin-like immunoreactivity was limited to fibers found largely in the juxtaglomerular region of the glomerular layer. In the deeper layers of the olfactory bulb, cholecystokinin-like immunoreactive fibers did not show any of branching or arborization that was evident in the juxtaglomerular region. Substance P-like immunoreactivity was seen in varicose fibers distributed in all of the human olfactory bulb laminae. In addition, stained multipolar neurons were found in the area of the anterior olfactory nucleus. Somatostatin-like immunoreactivity was similar to that of substance P in that a plexus of stained fibers was found in all laminae of the olfactory bulb. Also, somatostatin-like immunoreactive cell bodies were found in the area of the anterior olfactory nucleus. However, as compared to substance P, somatostatin had a less dense plexus of immunoreactive fibers in the olfactory bulb. These results increase our understanding of the fundamental organization of the human olfactory system. The current data, coupled with prior studies, provide a foundation from which to study the cellular pathology of diseases with known olfactory system sequelae such as Alzheimer's, Parkinson's, and schizophrenia.
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PMID:Immunohistochemical analyses of the human olfactory bulb. 769 Mar 71

The tissue distribution of somatostatin (SST) immunoreactivity was studied in the nasal and forebrain region in the chick embryo. On embryonic day (ED) 3, SST-immunoreactive (ir) cells were first detected in the cells migrating from the olfactory placode. Then, at ED3.5, SST-ir cells and -ir fibers appeared in the olfactory epithelium and olfactory nerve bundles. At ED6-8, one component of the SST-ir fibers was found to separate from the olfactory nerve and it entered the parenchyma of the medial forebrain surface. These SST-ir fibers extended dorsocaudally toward the preseptal area. During this same period, a few SST-ir cells were observed in the medial forebrain adjacent to the SST-ir fibers. SST immunoreactivity in the nasal and forebrain areas was most striking at ED5-8 but a reduction of SST immunoreactivity in the nasal and forebrain areas occurred at ED11 and it virtually disappeared by the day of hatching. These results indicate that the expression of SST in the nasal and forebrain regions is transient in the chick embryo. Since the SST-ir cells did not co-express luteinizing hormone-releasing hormone (LHRH), it, thus, appears that these SST-r cells belong to a different cell population from LHRH neurons that are also found in the olfactory-forebrain axis during embryonic development [23]. However, a close relationship exists between SST-ir cells and -ir neuronal fibers and LHRH neurons. This may play a role in development of LHRH neurons.
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PMID:Transient expression of somatostatin immunoreactivity in the olfactory-forebrain region in the chick embryo. 784 15

Material for the study came from one 126 day-old rhesus monkey fetus and two 3 day-old neonates. The immunocytochemical detection of somatostatin, neurotensin (NT), parvalbumin, calbindin D-28K, DARPP-32 as well as tyrosine hydroxylase (TH), dopamine-beta-hydroxylase and serotonin (5-HT), was carried out on serial cryostat sections of the entorhinal cortex. The authors reported in a previous paper the precocious differentiation of the entorhinal cortex in rhesus monkey fetuses and featured the conspicuous expression of calbindin D-28K, somatostatin, neurotensin, and the monoaminergic innervation during the first half of gestation. The present study shows distinct temporal profiles of neurochemical development during the second half of gestation: the dense neuropeptidergic innervation remained a constant feature; the three aminergic systems gradually increased in density; parvalbumin, unlike calbindin D-28K, was primarily expressed during the last quarter of gestation. Three other prominent features of the last quarter of gestation are illustrated: the refinement of the modular neurochemical organization of the lamina principalis externa, the delayed chemoanatomical development of the rhinal sulcus area, and the establishment of a distinct rostrocaudal pattern of neurochemical distribution. In correspondence with the cluster-like organization of the lamina principalis externa, the authors observed in the olfactory, rostral, and intermediate fields of the neonate monkey entorhinal cortex, a particular subset of pyramidal-shaped neurons: located in layer III, they were characterized by fasciculated apical dendrites ascending between the cellular islands of the discontinuous layer II and the coexpression of calbindin D-28K and DARPP-32. Besides, most of the other chemical systems displayed a distinct, area-specific, patchy distribution, except for the homogeneously distributed noradrenergic innervation. In the olfactory and rostral fields, TH positive dopaminergic fibers accumulated on the neuronal islands of layers II-III, and parvalbumin labeled fibers on those of layer III, whereas patches of 5-HT and NT-like reactive terminals were segregated between the cellular islands, overlapping the DARPP-32/calbindin D-28 K labeled dendritic bundles. At the opposite, in the intermediate field, 5-HT positive terminals overlapped the cellular islands of layer II and thin fascicles of dopaminergic fibers ran in the inter island spaces. The somatostatin-LIR innervation was apparently too dense to reveal a patchy distribution that existed at earlier developmental stages. In the caudal field, the patchy pattern was replaced by a predominant bilaminar type of distribution of NT, 5-HT, and TH-like positive afferents.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurochemical development of the hippocampal region in the fetal rhesus monkey. II. Immunocytochemistry of peptides, calcium-binding proteins, DARPP-32, and monoamine innervation in the entorhinal cortex by the end of gestation. 791 99

Amplification of complementary DNA by the polymerase chain reaction and anti-peptide antibodies were used to characterize the expression of two alternatively spliced forms of a metabotropic glutamate receptor (mGluR1 alpha and mGluR1 beta) in the central nervous system of the rat. Polymerase chain reaction analysis showed that mGluR1 alpha was the predominate of the two forms in the cerebellum, diencephalon, mesencephalon, olfactory bulb and brainstem, while mGluR1 beta was the major form present in the hippocampus. Approximately equal amounts of the two receptors were expressed in the cerebral cortex, septum and striatum. Immunochemical analyses of the two receptors were conducted in the rat cerebellum and hippocampus. An mGluR1 alpha-specific antibody labelled a protein with a relative molecular weight of 146,000 on immunoblots of the hippocampus and cerebellum. Immunoblot analysis of the developmental expression of mGluR1 alpha in the hippocampus and cerebellum demonstrated that in both structures, the levels of mGluR1 alpha were at or near their maximum levels in the adult brain. In contrast, two mGluR1 beta-specific antibodies failed to detect mGluR1 beta on immunoblots of brain tissue, thus precluding an immunocytochemical analysis of this receptor. Although low levels of a higher-molecular weight protein, possibly a dimeric form of mGluR1 beta were seen with one of the mGluR1 beta-specific antibodies, we hypothesize that some of the mGluR1 beta present in brain tissue may undergo proteolytic cleavage of the carboxy terminus. Immunocytochemical analysis of mGluR1 alpha showed that very high levels of this receptor were expressed in Purkinje cell bodies and dendrites. In the granule cell layer, some Golgi neurons were immunostained. The granule cells were not labelled. In the hippocampus, mGluR1 alpha immunoreactivity was present in interneurons of the stratum oriens and the dentate hilar region. Double-labelling studies demonstrated that these interneurons were also immunopositive for the neuropeptide somatostatin. The presence of mGluR1 alpha in cells of the hippocampus that are associated with the release of somatostatin, suggest that this receptor could play a role in regulating hippocampal excitability in both normal and epileptic tissues.
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PMID:Characterization of two alternatively spliced forms of a metabotropic glutamate receptor in the central nervous system of the rat. 807 87

We report here on the cloning of a human intronless gene encoding a member of the G-protein linked somatostatin (SST) receptor subfamily, termed SSTR3. Based on the deduced amino acid sequence, this gene encodes a 418 amino acid protein displaying sequence similarity, particularly within putative transmembrane domains, with the recently cloned human SSTR1 (62%), SSTR2 (64%) and SSTR4 (58%) receptors. Membranes prepared from COS-7 cells transiently expressing the human SSTR3 gene bound [125I]Leu8,D-Trp22,Tyr25 SST-28 in a saturable manner with high affinity (approximately 200 pM) and with rank order of potency (D-Trp8 SST-14 > SST-14 > SMS-201-995 > SST-28) indicative of a somatostatin-14 selective receptor. The pharmacological profile of the expressed human SSTR3 receptor is similar but not identical to that reported for the rat homolog [(1992) J. Biol. Chem. 267, 20422] where the peptide selectivity is SST-28 > or = SST-14 >>> SMS-201-995. Northern blot analysis reveals the presence of an SSTR3 mRNA species of approximately 5 kb in various regions of the monkey brain, including the frontal cortex, cerebellum, medulla, amygdala, with little or no SSTR3 mRNA detectable in brain regions such as the striatum, hippocampus, and olfactory tubercle. The SSTR3 receptor gene maps to human chromosome 22. The existence of at least four distinct human genes encoding somatostatin-14 selective receptors with diverse pharmacological specificities may help to account for some of the multiple biological actions of somatostatin under normal and pathological conditions.
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PMID:A human somatostatin receptor (SSTR3), located on chromosome 22, displays preferential affinity for somatostatin-14 like peptides. 809 79

Based on pharmacological, biochemical, and molecular criteria, multiple somatostatin receptor (SSTR) subtypes selective for somatostatin (SST)-14 and -28 have been postulated to exist in both the brain and periphery. We report here on the cloning and characterization of a human gene encoding a new member of the guanine nucleotide-binding protein-linked SSTR family, termed human (h)SSTR4. The 388-amino acid protein, with a predicted molecular mass of approximately 42 kDa, displays sequence similarity, particularly within putative transmembrane domains, with the recently cloned hSSTR1 (69%), hSSTR2 (56%), and hSSTR3 (58%). Membranes prepared from COS-7 cells transiently expressing the hSSTR4 gene bound 125I-[Leu8,D-Trp22,Tyr25]SST-28 in a saturable manner with high affinity (approximately 60 pM) and with a pharmacological profile and rank order of potency ([D-Trp8]SST-14 > SST-14 > SMS 201-995 > SST-28 > MK-678) indicative of a SST-14-selective receptor. Ki values for the inhibition of 125I-[Leu8,D-Trp22,Tyr25]SST-28 binding to the expressed receptor by these somatostatinergic peptides were 0.3, 1.1, 1.4, 2.2, and 6.5 nM, respectively. High affinity agonist binding to hSSTR4 was significantly reduced by GTP and pertussis toxin, indicating association of the expressed receptor with pertussis toxin-sensitive guanine nucleotide-binding proteins. Northern blot analysis revealed the presence of an SSTR4 mRNA species of approximately 4 kilobases in select regions of the monkey brain, including the hippocampus, hypothalamus, cortex, and striatum, with little or no receptor mRNA detected in either the olfactory tubercle, medulla, cerebellum, or amygdala. The SSTR4 gene maps to human chromosome 20. These findings document the existence of a novel human SSTR gene. Although the hSSTR4 displays an overall deduced amino acid homology of 86% with the recently reported rat homolog [Proc. Natl. Acad. Sci. USA 89:11151-11155 (1992)], the two gene products possess distinctive pharmacological profiles and affinities for the SST agonists SMS 201-995 and MK-678.
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PMID:Cloning and expression of a human somatostatin-14-selective receptor variant (somatostatin receptor 4) located on chromosome 20. 810 Mar 52

The identification of high-affinity binding sites for neuropeptides on individual target cells is a prerequisite when studying the sites of action and the manner in which peptides act as neuromediators. In situ and in vitro, this can be achieved using newly synthesized, biologically active conjugates of somatostatin or cholecystokinin (sulphated octapeptide) with colloidal gold. Labelled neurons show a peptide-specific, non-overlapping distribution in rat telencephalic structures; i.e, whereas the somatostatin-gold conjugate labels binding sites on neurons and glial cells, cholecystokinin-binding sites are restricted to neurons. Binding of either gold-labelled ligand can be competitively suppressed by excess amounts of the native peptide or its analogues. Neuronal somatostatin-binding sites are visualized on neurons in lamina III and, in particular, in lamina V/VI of the primary somatosensory cortex and in the magnocellular nucleus of the telencephalic cholinergic system. Cholecystokinin-binding sites are localized in the main olfactory bulb, on neurons in the cortical "hindlimb" and "forelimb" region, in the hippocampus, and in the cingulate and visual cortex.
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PMID:Visualization of neuropeptide-binding sites on individual telencephalic neurons of the rat. 810 69

In situ hybridization histochemistry was performed to analyse the distribution of the messenger RNA (mRNA) of three putative somatostatin (SRIF) receptors in rat brain, using oligonucleotide probes derived from the cDNA coding for SSTR-1, SSTR-2, and SSTR-3 receptors. SSTR-1 signals were found in layers V-VI of the cerebral cortex, in primary olfactory cortex, taenia tecta, subiculum, entorhinal cortex, granular layer of the dentate gyrus, amygdala and cerebellar nuclei. Signals for SSTR-2 were found in the frontal cerebral cortex (layers IV, V and VI), taenia tecta, claustrum, endopiriform nucleus, locus coeruleus, medial habenula, subiculum, granular cell layer of the dentate gyrus and amygdala. High levels of SSTR-3 hybridization were found in the olfactory bulb, primary olfactory cortex, islands of Calleja, medial habenula, amygdala, granular layer of the dentate gyrus, various thalamic and pontine nuclei and in the granular and Purkinje cell layers of the cerebellum. The distribution of the hybridization signals of the oligoprobes is consistent with the labelling of specific SRIF binding sites in rat brain. Especially, SSTR-2 and SSTR-1 oligos seem to label regions in which SS-1 and SS-2 receptors, respectively, have been previously characterized in autoradiographical studies. The situation is less clear with SSTR-3 mRNA, since SRIF binding in adult rats is usually low or absent in cerebellum, although some cerebellar nuclei appear to be labelled in the adult. The localization of SSTR-1, SSTR-2 and SSTR-3 mRNAs suggests that SRIF receptor subtypes in rat brain show profound differences in their distribution and are involved in a variety of central, in addition to neuroendocrine, functions.
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PMID:Localization of somatostatin (SRIF) SSTR-1, SSTR-2 and SSTR-3 receptor mRNA in rat brain by in situ hybridization. 817 Apr 98

The present study demonstrates cell-specific distribution and describes distinct functional regulation of different adenylyl cyclases (AC, types I-VI) in rat pituitary cell tumor cell lines (GH12C1, GH3 and GH4C1 cells) and pituitary tissue. Northern-blot analysis revealed a distinct pattern of cell-specific expression of the different AC types; Ca2+/calmodulin (CaM)-insensitive AC type II was found in all cell lines tested except GH(1)2C1 cells. The Ca(2+)-inhibitable AC type VI was found in all cell types tested. We observed a lack of the Ca2+/CaM-sensitive AC type I in GH3 and GH4C1 cells. GH(1)2C1 cells exclusively contained both Ca2+/CaM-sensitive AC types I and III, the latter previously believed to be specific for olfactory tissue. An additional transcript of AC type III was found in rat brain and rat liver tissue. AC type IV, which is Ca2+/CaM insensitive, could be detected in the prolactin-producing GH3 and GH4C1 cells and pituitary tissue but not in growth-hormone-producing GH(1)2C1 cells. Basal and vasoactive-intestinal-peptide-(VIP)-releasing-hormone, somatostatin (SRIF) and thyrotropin-releasing-hormone (TRH)-modulation of AC activity was measured in the presence of 100 microM EGTA, anti-CaM serum (dilution 1:2000) or 10 microM trifluoroperazine. Antisera against guanine-nucleotide-binding protein (G-protein) alpha subunits (G(i)-2 alpha, Gs alpha) and beta subunits (G beta 35/36) and CaM were added for functional studies of the SRIF and VIP-modulated AC in GH(1)2C1 and GH3 cells. These experiments indicate that the VIP and the SRIF receptors are coupled to a Ca2+/CaM-sensitive AC in GH(1)2C1 cells, different from the AC involved in the regulation of cAMP levels in GH3 and GH4C1 cells. In addition, the beta gamma-complex is possibly able to modulate SRIF-inhibited AC activity by potentiating the inhibitory effect. The TRH receptor in GH3 and GH4C1 cells is coupled to a Ca2+/CaM-sensitive AC which is different from the already cloned forms of AC types I and III. We, therefore, conclude that hormone regulation of pituitary tumour cell functions differs between the GH cell lines, due to specific utilisation of AC types.
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PMID:Cell-specific expression and function of adenylyl cyclases in rat pituitary tumour cell lines. 820 Mar 59

The tissue distribution of mRNA encoding five somatostatin receptor subtypes, SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5, was determined in adult rat tissues by solution hybridization/nuclease protection analysis using sequence-specific cRNA probes. In the central nervous system, SSTR1 and SSTR2 mRNA were expressed widely, with highest levels in hippocampus, hypothalamus, cortex, and amygdala and expression of both isoforms in cerebellum and spinal cord. Expression of SSTR3 was also widespread, occurring in all brain regions examined, with the highest level of expression in the cerebellum. SSTR4 mRNA was detected in most brain regions, with highest levels occurring in the hippocampus, cortex, and olfactory bulb. No detectable levels were found in cerebellum. SSTR5 showed a unique pattern of expression in the central nervous system, being found primarily in the hypothalamus and preoptic area. In peripheral tissues, high levels of SSTR1 and SSTR2 mRNA were found in pituitary and spleen. SSTR1 mRNA was also found in the heart and intestine, SSTR2 was detected in pancreas, and both isoforms were expressed in stomach. Expression of SSTR3 was noted in heart, liver, stomach, intestine, kidney, spleen, and pituitary. The patterns of expression were similar for SSTR4 and SSTR3 mRNA; however, SSTR4 was not expressed in liver. SSTR5 was expressed predominantly in the pituitary, but detectible levels were observed in spleen and intestine. Thus, the SSTR subtype mRNA showed both a tissue-specific and overlapping pattern of expression. Taken together with SSTR-specific signal transduction systems, this probably explains the diverse physiological actions of somatostatin.
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PMID:Tissue distribution of somatostatin receptor subtype messenger ribonucleic acid in the rat. 824 78

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