Selective agonism in somatostatin receptor signaling and regulation

Schönbrunn, Agnes

doi:10.1016/j.mce.2007.09.009

Cited by 51 publications

(44 citation statements)

References 42 publications

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“…Moreover, it has been suggested that different SSA, in the same cell type, may elicit differential effects, due to the activation of different subsets of intracellular mediators. This phenomenon, also named biased agonism, seems to depend on the typical agonist-receptor interactions (Schonbrunn 2008, Ben-Shlomo et al 2009, Cescato et al 2010. In two recent in vitro studies octreotide and pasireotide (SOM 230) have been demonstrated to modulate sst 2A receptor phosphorylation and trafficking in a clearly distinct manner, despite their approximately similar binding affinity to this SSTR subtype (Poll et al 2010).…”

Section: Ss and Da Analogs Treatment In Endocrine Tumorsmentioning

confidence: 99%

“…The intracellular pathways activated by SSTR activation appear different in different types of tumor cells and depend on the specific SSTR distribution pattern, signaling elements, as well as to receptor desensitization, internalization, and cross talk (Lahlou et al 2004, Schonbrunn 2008. Moreover, it has been suggested that different SSA, in the same cell type, may elicit differential effects, due to the activation of different subsets of intracellular mediators.…”

Section: Ss and Da Analogs Treatment In Endocrine Tumorsmentioning

confidence: 99%

“…SS binding to SSTR subtypes activates a series of second messenger systems, resulting in the inhibition of calcium channels and adenylate cyclase activity, ultimately leading to inhibition of hormone secretion (Reisine & Bell 1995, Patel 1997, 1999. Stimulation of other second messengers, such as phosphotyrosine phosphatases (PTPs), plays a role in SS-and somatostatin analogs (SSA)-mediated control of cell growth (Schally 1988, Lamberts et al 1991, Hofland et al 1995, Patel 1999, Hofland & Lamberts 2003, Florio 2008, Schonbrunn 2008. Among the SSTR, sst 3 appears to be the subtype mostly related to the pro-apoptotic and antiproliferative effects of SS and SSA (Ferone et al 2002, Hofland & Lamberts 2003.…”

Section: Introductionmentioning

confidence: 99%

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The role of somatostatin and dopamine D2 receptors in endocrine tumors

Gatto¹,

Hofland²

2011

Endocrine-Related Cancer

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Somatostatin (SS) and dopamine (DA) receptors have been highlighted as two critical regulators in the negative control of hormonal secretion in a wide group of human endocrine tumors. Both families of receptors belong to the superfamily of G protein-coupled receptors and share a number of structural and functional characteristics. Because of the generally reported high expression of somatostatin receptors (SSTRs) in neuroendocrine tumors (NET), somatostatin analogs (SSA) have a pronounced role in the medical therapy for this class of tumors, especially pituitary adenomas and well-differentiated gastroenteropancreatic NET (GEP NET). Moreover, NET express not only SSTR but also frequently dopamine receptors (DRs), and DA agonists targeting the D 2 receptor (D 2 ) have been demonstrated to be effective in controlling hormone secretion and cell proliferation in in vivo and in vitro studies. The treatment with SSAs combined with DA agonists has already been demonstrated efficacious in a subgroup of patients with GH-secreting pituitary adenomas and few reported cases of carcinoids. The recent availability of new selective and universal SSA and DA agonists, as well as the chimeric SS/DA compounds, may shed new light on the potential role of SSTR and D 2 as combined targets for biotherapy in NET. This review provides an overview of the latest studies evaluating the expression of SSTR and DR in NET, focusing on their co-expression and the possible clinical implications of such co-expression. Moreover, the most recent insights in SSTR and D 2 pathophysiology and the future perspectives for treatment with SSA, DA agonists, and SS/DA chimeric compounds are discussed.

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Section: Ss and Da Analogs Treatment In Endocrine Tumorsmentioning

confidence: 99%

Section: Ss and Da Analogs Treatment In Endocrine Tumorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The role of somatostatin and dopamine D2 receptors in endocrine tumors

Gatto¹,

Hofland²

2011

Endocrine-Related Cancer

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“…The main structural and functional features of ssts, including their pharmacology, signalling, endocytosis and recycling, have been extensively characterized using both primary cell cultures and, specially, cell lines stably transfected with different receptors from diverse species, and this information has been carefully reviewed (Moller et al, 2003;Jacobs and Schulz, 2007;Schonbrunn, 2007;Siehler et al, 2007, in …”

Section: Homodimerization Of Somatostatin Receptorsmentioning

confidence: 99%

Dimerization of G protein-coupled receptors: New avenues for somatostatin receptor signalling, control and functioning

Durán-Prado

Malagón

Gracia‐Navarro

et al. 2008

Molecular and Cellular Endocrinology

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Somatostatin acts through binding and activation of five G protein coupled receptors (GPCRs) termed somatostatin receptors or ssts (sst1-sst5). These receptors, as many other GPCRs are not just monomers but display a differential tendency to homodimerize, which varies depending on the sst subtype. Moreover, there is evidence that pairs of distinct receptors such as ssst2-sst3 and sst1-sst5 crosstalk by establishing a physical interaction, which results in altered pharmacological or/and functional properties. In addition, ssts can also heterodimerize with other families of GPCRs, as opioid and dopamine receptors, originating heterodimers which properties are different to those of their separated receptors. The present review summarizes the current knowledge on ssts homodimerization, heterodimerization, and interaction with other GPCRs, as well as how interactions affect different aspects of the normal functioning of these receptors.

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“…[23,24,26] Nevertheless, the natural ligands of SSTR1-5 can bind all somatostatin receptors with high affinity.…”

Section: Short Synthetic Analogues Of Somatostatinmentioning

confidence: 99%

Medical therapy for advanced gastro-entero-pancreatic and bronchopulmonary neuroendocrine tumors

Torniai¹,

Rinaldi²,

Morgese³

et al. 2016

JCMT

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Neuroendocrine tumors (NETs) represent a spectrum of rare neoplasms arising in different organism sites. Depending on the site of onset, they also can be distinguished using lab exams (secreting vs. nonsecreting), clinical symptoms (functioning vs. nonfunctioning), behavioral, morphological characteristics (tumor cells' architectural growth patterns, mitotic and Ki-67 index, presence of necrosis), and grade of cellular differentiation. The aim of this review is to focus on the main signaling pathways targeted by medical treatments of advanced sporadic gastro-entero-pancreatic (GEP) and bronchopulmonary (BP) neuroendocrine neoplasms. The scientific literature regarding treatment of advanced GEP and BP-NETs has been extensively reviewed using MEDLINE and PubMed databases, selecting principal and more recent research articles, clinical trials, and updated guidelines. Somatostatin analogues represent a valid approach to control symptoms in functioning tumors and to inhibit tumor progression in certain categories on the basis of the typical somatostatin receptor expression observed in NETs. The pathogenesis of NETs has been the subject of increased interest in recent years. Many driver mutations pathway genes have been identified as important factors in the carcinogenesis process and, therefore, as potential targets for new anticancer therapies. Activating mutations have been shown in epidermal growth factor receptor, stem cell factor receptor, platelet-derived growth factor receptor, vascular endothelial growth factor, basic-fibroblastic growth factor, transforming growth factor, insulin-like growth factor-1, and their receptors. Effective M-Tor inhibition pathway modulation has led to the approval of drugs in this field such as everolimus. New drugs and several combination regimens with targeted and newer biological agents are being developed and tested in recently conducted and ongoing trials.

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Selective agonism in somatostatin receptor signaling and regulation

Cited by 51 publications

References 42 publications

The role of somatostatin and dopamine D2 receptors in endocrine tumors

The role of somatostatin and dopamine D2 receptors in endocrine tumors

Dimerization of G protein-coupled receptors: New avenues for somatostatin receptor signalling, control and functioning

Medical therapy for advanced gastro-entero-pancreatic and bronchopulmonary neuroendocrine tumors

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