Molecular Signaling of Somatostatin Receptors

Lahlou, Hicham; Guillermet, J; Hortala, Marylis; Vernejoul, Fabienne; Pyronnet, Stéphane; Bousquet, Corinne; Susini, Christiane

doi:10.1196/annals.1294.012

Cited by 135 publications

(104 citation statements)

References 66 publications

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“…The binding of hormone to somatostatin receptors initiates a complex set of signaling events triggered by the interaction of the activated receptors with a large number of different protein partners (for recent reviews see (Csaba and Dournaud, 2001;Lahlou et al, 2004;Olias et al, 2004;Schonbrunn, 2004), reviews in this compendium). As members of the seventransmembrane domain receptor family, it is not surprising that much of somatostatin receptor signaling involves activation of heterotrimeric G proteins.…”

Section: Somatostatin Receptor Signaling and Regulation Involve Multimentioning

confidence: 99%

Selective agonism in somatostatin receptor signaling and regulation

Schönbrunn¹

2008

Molecular and Cellular Endocrinology

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SummaryThe five somatostatin receptor subtypes, named sst1 to sst5, activate both distinct and common signaling pathways and exhibit different patterns of receptor regulation. Until recently it was believed that once a particular somatostatin receptor was activated by an agonist, all the downstream signaling and regulatory effects characteristic of that receptor subtype in that cellular environment would be triggered. Thus, differences in the actions of somatostatin analogs between tissues were attributed to variability in the nature and concentration of the sst receptor subtypes and effectors expressed in different targets. However, agonists have recently been shown to exhibit functional selectivity at individual sst receptors such that they can elicit a subset of that receptor's potential effects, a property known as biased agonism. This review will summarize the evidence for functionally selective somatostatin receptor agonists and discuss the implications and promise of these new findings.

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Section: Somatostatin Receptor Signaling and Regulation Involve Multimentioning

confidence: 99%

Selective agonism in somatostatin receptor signaling and regulation

Schönbrunn¹

2008

Molecular and Cellular Endocrinology

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“…In particular, SS inhibits pituitary GH and TSH secretion and insulin, glucagon, and secretin secretion at gastro-entero-pancreatic level (Van Op den Bosch et al 2009, Reubi & Schonbrunn 2013. These effects are mediated by five receptor subtypes (SST1-5) belonging to the G protein coupled receptors superfamily (GPCR) that differ in tissue distribution, affinity to ligands and mechanisms of action and regulation (Patel 1998, Lahlou et al 2004. As demonstrated in cells transfected with different receptor subtypes and confirmed by the clinical use of selective agonists, SST2 and to lesser extent SST5 and SST3 appear to mediate most of the antisecretive and antiproliferative effects of SS (Reubi & Schonbrunn 2013).…”

Section: Introductionmentioning

confidence: 99%

Filamin-A is required to mediate SST2 effects in pancreatic neuroendocrine tumours

Vitali

Cambiaghi

Zerbi

et al. 2016

Endocrine-Related Cancer

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Somatostatin receptor type 2 (SST2) is the main pharmacological target of somatostatin (SS) analogues widely used in patients with pancreatic neuroendocrine tumours (P-NETs), this treatment being ineffective in a subset of patients. Since it has been demonstrated that Filamin A (FLNA) is involved in mediating GPCR expression, membrane anchoring and signalling, we investigated the role of this cytoskeleton protein in SST2 expression and signalling, angiogenesis, cell adhesion and cell migration in human P-NETs and in QGP1 cell line. We demonstrated that FLNA silencing was not able to affect SST2 expression in P-NET cells in basal conditions. Conversely, a significant reduction in SST2 expression (K43G21%, P!0.05 vs untreated cells) was observed in FLNA silenced QGP1 cells after long term SST2 activation with BIM23120. Moreover, the inhibitory effect of BIM23120 on cyclin D1 expression (K46G18%, P!0.05 vs untreated cells), P-ERK1/2 levels (K42G14%; P!0.05 vs untreated cells), cAMP accumulation (K24G3%, P!0.05 vs untreated cells), VEGF expression (K31G5%, P!0.01 vs untreated cells) and in vitro release (K40G24%, P!0.05 vs untreated cells) was completely lost after FLNA silencing. Interestingly, BIM23120 promoted cell adhesion (C86G45%, P!0.05 vs untreated cells) and inhibited cell migration (K24G2%, P!0.00001 vs untreated cells) in P-NETs cells and these effects were abolished in FLNA silenced cells. In conclusion, we demonstrated that FLNA plays a crucial role in SST2 expression and signalling, angiogenesis, cell adhesion and cell migration in P-NETs and in QGP1 cell line, suggesting a possible role of FLNA in determining the different responsiveness to SS analogues observed in P-NET patients.

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“…Physiological responses vary with the expression of individual receptor subtypes that are functionally coupled to the effectors of signal transduction, resulting in physiological impact. 20 Within the context of this study, SSTR4 was uniquely expressed by HOCs within the liver. The expression of SSTR4 in rat liver has not been observed previously.…”

Section: Discussionmentioning

confidence: 99%

“…Somatostatin receptors (SSTRs) are widely distributed throughout many tissues and show different functions in various cell and tissue types. 18,20 However, studies on receptor expression in various tumors reveal inconsistencies, which are also observed in rat liver studies. 21,22 Reynaert et al 22 reported the presence of SSTRs 1-3 in activated hepatic stellate cells in CCl 4 -treated rats, but not in normal rat liver.…”

mentioning

confidence: 97%

A potential role of somatostatin and its receptor SSTR4 in the migration of hepatic oval cells

Jung

Zheng

et al. 2006

Laboratory Investigation

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Somatostatin (SST) is a regulatory peptide that activates G protein-coupled receptors comprised of five members (somatostatin receptors (SSTRs) 1-5). Despite the broad use of SST and its analogs in clinical practice, the spectrum of SST activities has been incompletely defined. Recently, it has been demonstrated that SST can be a chemoattractant for hematopoietic precursor cells. Since hepatic oval cells (HOCs) share common characteristics with hematopoietic stem cells, we hypothesized that SST could act as a chemoattractant for HOCs by stimulating SSTRs. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot assay revealed an increased expression of SST in the 2-acetyl-aminofluorene (2AAF)/partial hepatectomy (PHx) HOC induction model. Immunohistochemical staining showed the expression of SST in 2AAF/PHx-treated rat liver, as compared to normal liver. Proliferation and migration assays demonstrated that the increase of SST was related to migration of HOCs, but not their proliferation. RT-PCR and quantitative real-time PCR showed that SSTR4 was preferentially expressed by HOCs. Western blot assay and immunohistochemical staining confirmed the expression of SSTR4 by HOCs. In addition, pretreatment with anti-SSTR4 antibody cultures resulted in a dramatic reduction of cell migration as compared to that of control. Lastly, SST stimulated the rearrangement of actin filaments in HOCs, while HOCs treated with anti-SSTR4 antibody failed to do so. These results suggest a positive role for SST in the migration of HOCs, and that this effect is mediated through SSTR4.

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Molecular Signaling of Somatostatin Receptors

Cited by 135 publications

References 66 publications

Selective agonism in somatostatin receptor signaling and regulation

Selective agonism in somatostatin receptor signaling and regulation

Filamin-A is required to mediate SST2 effects in pancreatic neuroendocrine tumours

A potential role of somatostatin and its receptor SSTR4 in the migration of hepatic oval cells

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