Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In psoriasis and atopic dermatitis, the inflammatory events have neurogenic components and the neuropeptides modify the functions of immuno-active cells in the skin. Somatostatin is a neuropeptide with several neuroendocrine and immunomodulating properties and mediates its actions by five distinct subtypes of G-protein-coupled receptors (SSTR1-5). This study describes the distribution of SSTR1-5, analysed with immunohistochemistry, in psoriasis, atopic dermatitis and controls. Normal human skin and lesional skin from patients with psoriasis or atopic dermatitis showed many similarities, but also some differences, as regards SSTR expression. SSTR1-3 were strongly expressed in the epidermis of healthy skin, and in the skin of patients with psoriasis or atopic dermatitis. It is noteworthy that SSTR4 and 5 were strongly expressed in the epidermis of psoriasis patients, but weakly expressed in the epidermis of those with atopic dermatitis and normal skin. The intensity of the staining also varied considerably between the different layers of the epidermis, especially in psoriasis patients. In all cases, the dendritic cells, found mostly in the papillary and upper reticular dermis, showed a strong expression of SSTR1-4, but a weak expression of SSTR5. SSTR1-5 were strongly expressed in the sweat glands in all skin biopsies. Hair follicles and sebaceous glands expressed all five subtypes. Striated muscle fibres showed an intense positive expression of SSTR1-4, but a weak or negative expression of SSTR5. The wide distribution and expression pattern of all five SSTRs in human skin suggest that somatostatin is involved in the interactions between the nervous system and the skin.
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PMID:Expression pattern of somatostatin receptor subtypes 1-5 in human skin: an immunohistochemical study of healthy subjects and patients with psoriasis or atopic dermatitis. 1708 61

The secretion of growth hormone (GH) is inhibited by hypothalamic somatostatin (SRIF) in somatotropes through five subtypes of the somatostatin receptor (SSTR1-SSTR5). We aimed to characterize the subtype(s) of SSTRs involved in the Ca2+ current reduction in GH3 somatotrope cells using specific SSTR subtype agonists. We used nystatin-perforated patch clamp to record voltage-gated Ca2+ currents, using a holding potential of -80 mV in the presence of K+ and Na+ channel blockers. We first established the presence of T-, L-, N-, and P/Q-type Ca2+ currents in GH3 cells using a variety of channel blockers (Ni+, nifedipine, omega-conotoxin GVIA, and omega-agatoxin IVA). SRIF (200 nM) reduced L- and N-type but not T- or P/Q-type currents in GH3 cells. A range of concentrations of each specific SSTR agonist was tested on Ca2+ currents to find the maximal effective concentration. Activation of SSTR2 with 10(-7) and 10(-8) M L-797,976 decreased the voltage-gated Ca2+ current and abolished any further decrease by SRIF. SSTR1, SSTR3, SSTR4, and SSTR5 agonists at 10(-7) M did not modify the voltage-gated Ca2+ current and did not affect the Ca2+ current response to SRIF. These results indicate that SSTR2 is involved mainly in regulating voltage-gated Ca2+ currents by SRIF, which contributes to the decrease in intracellular Ca2+ concentration and GH secretion by SRIF.
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PMID:Somatostatin decreases voltage-gated Ca2+ currents in GH3 cells through activation of somatostatin receptor 2. 1732 72

Despite our knowledge of somatostatin (SOM) in gastrointestinal functions, little information is available on the SOM receptors (SSTRs) mediating these effects. This study focussed on the expression of SSTRs in non-inflamed and Schistosoma mansoni-infected murine ileum using immunocytochemistry, reverse transcriptase (RT)-PCR and quantitative real time RT-PCR (qPCR). In the non-inflamed ileum, SSTRs showed a widespread, cell-type specific expression pattern. For instance, SSTR2A immunoreactivity was detected in a minor population of submucous but not myenteric glial cells. In the inflamed ileum, significant changes in the expression pattern of SSTRs occurred, with SSTR1 and SSTR3 expression on mucosal mast cells (MMCs) and mucosal nerve fibres. SSTR4-immunoreactive nerve fibres were detected in granulomas and the lamina propria. qPCR experiments indicated significantly increased mRNA levels for SOM, SSTR1 and SSTR3 in inflamed ileum. This study reveals that SSTRs are expressed in specific cell types in murine ileum. Expression of SSTR1 and SSTR3 on MMCs and increased density of SOM-expressing nerve fibres in the lamina propria during inflammation, support the hypothesis that SOM is implicated in the physiological control of MMCs during intestinal inflammation. Evidence is provided that in mouse mainly SSTR1, SSTR3 and SSTR4 are involved in the somatostatinergic inflammatory effects during intestinal schistosomiasis.
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PMID:Effect of intestinal inflammation on the cell-specific expression of somatostatin receptor subtypes in the murine ileum. 1759 41

The hypothalamus is a major site of somatostatin (SST) production and action. SST is synthesized in several hypothalamic nuclei and involved in a variety of functions. Using SST receptor (SSTR)-specific antibodies, we localized SSTR subtypes in the rat hypothalamus. In addition, we also demonstrated SSTRs colocalization with SST, NADPH-diaphorase (NADPH-d), and tyrosine hydroxylase (TH). SSTR1 is strongly localized in neurons in all major hypothalamic nuclei as well as in nerve fibers in the zona externa of the median eminence and the ependyma of the third ventricle. SSTR2 is also well expressed in most regions but with a relatively lower abundance in comparison to SSTR1. In contrast, SSTR3 is localized primarily in the paraventricular nucleus, dorsomedial hypothalamic nucleus, arcuate nucleus, and median eminence. SSTR4-like immunoreactivity is mainly confined to the arcuate nucleus, ventromedial hypothalamic nucleus, median eminence, and ependymal cells of third ventricle, with the rare SSTR4-positive neuron in the paraventricular nucleus. SSTR5 is the least expressed subtype occurring only in few cells in the inner layer of the median eminence. Overall, SSTR1 is the predominant subtype, followed by SSTR2, 4, 3, and 5. Combined immunofluorescence, immunocytochemistry, and histochemistry were used to demonstrate SSTRs colocalization with SST, TH, and NADPH-d. SSTRs colocalization with SST, TH, and NADPH-d displays in a region and receptor specificity. Colocalization of SST and NADPH-d with SSTRs in hypothalamic regions was similar, suggesting that SST and NADPH-d producing cells are same. In contrast, TH was selectively coexpressed with SSTRs in the hypothalamus in a receptor-specific manner. Taken together, these data suggest that SSTRs may interact with NADPH-d and TH to exert a physiological role in concert within the hypothalamus.
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PMID:Colocalization of somatostatin receptor subtypes (SSTR1-5) with somatostatin, NADPH-diaphorase (NADPH-d), and tyrosine hydroxylase in the rat hypothalamus. 1762 71

1. Growth hormone (GH) secretion from pituitary somatotropes is mainly regulated by two hypothalamic hormones, GH-releasing hormone (GHRH) and somatotrophin releasing inhibitory factor (SRIF). 2. Somatotrophin releasing inhibitory factor inhibits GH secretion via activation of specific membrane receptors, somatostatin receptors (SSTRs) and signalling transduction systems in somatotropes. 3. Five subtypes of SSTRs, namely SSTR1, 2, 3, 4 and 5, have been identified, with the SSTR2 subtype divided into SSTR2A and SSTR2B. All SSTRs are G-protein-coupled receptors. 4. Voltage-gated Ca(2+) and K(+) channels on the somatotrope membrane play an important role in regulating GH secretion and SRIF modifies both channels to reduce intracellular free Ca(2+) concentration and GH secretion. 5. Using specific SSTR subtype-specific agonists, it has been found that reduction in Ca(2+) currents by SRIF is mediated by SSTR2 and an increase in K(+) currents is mediated by both SSTR2 and SSTR4 in rat somatotropes.
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PMID:Involvement of somatostatin receptor subtypes in membrane ion channel modification by somatostatin in pituitary somatotropes. 1789 6

Using peptide affinity purification, we identified an interaction between somatostatin receptors SSTR4 and SSTR1 and PDZ domains 1 and 2 of the postsynaptic proteins postsynaptic density protein of 95kDa (PSD-95) and PSD-93. The existence of the SSTR4/PSD-95 complex was verified by coimmunoprecipitation from transfected cells and solubilized brain membranes. In neurons, dendritically localized SSTR4 partially colocalizes with postsynaptic PSD-95. As functional parameters of the receptor, such as coupling to potassium channels, are not affected by the interaction with PSD-95, the association may serve to localize the receptor to postsynaptic sites.
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PMID:Interaction of brain somatostatin receptors with the PDZ domains of PSD-95. 1795 Jul 29

Conventional chemotherapy has no role to play in the curative treatment of laryngeal carcinoma, yet the mortality rate from advanced disease has improved little over the last 20 years. Somatostatin is a naturally occurring peptide, which exerts anti-proliferative and anti-angiogenic effects via 5 membrane-bound receptor subtypes (SSTRs 1-5). We have previously studied the expression of SSTRs 1 and 2 and demonstrated loss of SSTR2 in laryngeal carcinoma. This study was therefore undertaken to study the expression of the remaining SSTR subtypes in laryngeal pathology. The expression of SSTRs 3, 4 and 5 was studied in benign (Reinke's oedema), pre-malignant and malignant laryngeal specimens using immunohistochemistry. There was very little expression of SSTR3, with low to moderate levels detected in just 1/6 (17%) benign and pre-malignant specimens and 3/12 (25%) malignant laryngeal tumours. A variable degree of SSTR4 expression was detected across the three groups, with low to moderate levels in 3/6 (50%) benign specimens, compared to only 1/6 (17%) pre-malignant specimens but 8/12 (67%) malignant laryngeal tumours. The majority of all specimens, however, demonstrated moderate to high levels of expression of SSTR5. This receptor was detected in 4/6 (67%) benign, all pre-malignant (100%) and 10/12 (83%) malignant cases. All the laryngeal carcinomas studied expressed either SSTR4 or SSTR5, with 60% expressing both, but very few expressing SSTR3. Somatostatin receptors warrant further investigation to determine whether they have a therapeutic role in carcinoma of the larynx.
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PMID:The expression of somatostatin receptors 3, 4 and 5 in laryngeal pathology. 1806 72

During the course of this study, we sought examine whether the expression of somatostatin receptors (SSTRs) is altered in the hippocampus following pilocarpine-induced status epilepticus (SE) in order to understand the role/function of SSTRs in the hippocampus after epileptogenic insults. SSTR1 and SSTR4 immunoreactivities were increased in the hippocampus at 1 week after SE. At 4 weeks after SE, SRIF1-family (SSTR 2A, SSTR2B, and SSTR5) immunoreactivity was increased only in neuropil. Both SSTR2A and 2B immunoreactivities were increased in CA2-3 pyramidal cells. However, SSTR3 and SSTR4 immunoreactivities were reduced in the CA1 pyramidal cells of epileptic rat due to neuronal loss. In addition, SSTR5 immunoreactivity was reduced in CA2 pyramidal cells and various interneurons. Both SSTR2B and SSTR4 immunoreactivities were increased within microglia following SE. Our findings suggest that increases in neuron-glial SSTR expressions may be closely related to the enhanced inhibition of the dentate gyrus and regulation of reactive microgliosis in the hippocampus of a pilocarpine model of temporal lobe epilepsy.
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PMID:The expression of somatostatin receptors in the hippocampus of pilocarpine-induced rat epilepsy model. 1895 27

Somatostatin analogs and dopamine agonists are clinically used for medical therapy of functioning pituitary tumors, such as growth hormone- and prolactin-secreting tumors, however, their effects on ACTH-secreting tumors are controversial. This study was aimed to determine whether somatostatin receptor (SSTR) subtype (1-5) and dopamine receptor type 2 (D2R) are differentially expressed in pituitary tumors causing Cushing's disease (CD), silent corticotroph adenoma (SCA), and non-functioning pituitary tumor (NFT). Tissue specimens were obtained from 35 pituitary tumors during transsphenoidal surgery. The steady-state mRNA levels of SSTR1-5 and D2R genes were determined by real-time reverse-transcription polymerase chain reaction. Both SSTR1 and 2 mRNA levels in SCA were greater than CD, while SSTR1 mRNA levels, but not SSTR2, in SCA were also greater than NFT. SSTR5 mRNA levels in CD were greater than SCA, but did not differ between NFT and SCA. SSTR4 mRNA expression was undetectable. D2R mRNA levels were markedly lower in CD and SCA than in NFT. The present study suggests that somatostatin analogs more selective for SSTR5 and for SSTR1 and/or 2may have the therapeutic potential for medical treatment of CD and SCA, respectively, whereas clinical application of dopamine agonists selective for D2R is very limited in either CD or SCA.
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PMID:Differential expression of somatostatin and dopamine receptor subtype genes in adrenocorticotropin (ACTH)-secreting pituitary tumors and silent corticotroph adenomas. 1931 29

About one-third of acromegalics are resistant to the clinically available somatostatin analogs (SA). The resistance is related to density reduction or different expression of somatostatin receptor subtypes (SSTR). This study analyzes SSTR's expression in somatotrophinomas, comparing to SA response, hormonal levels, and tumor volume. We analyzed 39 somatotrophinomas; 49% were treated with SA. The most expressed SSTR was SSTR5, SSTR3, SSTR2, SSTR1, and SSTR4, respectively. SSTR1 and SSTR2 had higher expression in patients that had normalized GH and IGF-I. SSTR3 was more expressed in patients with tumor reduction. There was a positive correlation between the percentage of tumor reduction and SSTR1, SSTR2 and SSTR3 expression. Also, a positive correlation between SSTR2 mRNA expression and the immunohistochemical reactivity of SSTR2 was found. Our study confirmed the association between the SA response to GH and IGF-I and the SSTR2. Additionally, this finding was also demonstrated in relation to SSTR1.
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PMID:Acromegaly: correlation between expression of somatostatin receptor subtypes and response to octreotide-lar treatment. 1933 Apr 52


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