SST3-selective potent peptidic somatostatin receptor antagonists

Reubi, Jean Claude; Schaer, Jean‐Claude; Wenger, Sandra; Hoeger, Carl; Érchegyi, Judit; Waser, Beatrice; Rivier, Jean

doi:10.1073/pnas.250483897

Cited by 92 publications

(103 citation statements)

References 47 publications

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“…Peptides were synthesized as described (18,19). Radioactive or nonradioactive metals were chelated to the DOTAcoupled sst 3 -ODN-8, DOTA-NOC, DOTA-sst 2 -ANT, and DTPA-TATE, as described (21).…”

Section: Methodsmentioning

confidence: 99%

“…Forskolin-stimulated cAMP accumulation was determined in CCL-sst 2 and -sst 3 cells by using a commercially available cAMP scintillation proximity assay, as described (18). sst2 and sst3 Receptor Internalization.…”

Section: Methodsmentioning

confidence: 99%

“…First, sst 3 is characterized by very efficient internalization properties (17). Second, recently, sst 3 -selective antagonists with high binding affinity but without triggering receptor internalization have been described (18). Their radiolabeled derivatives may be used as antagonist radioligands in case the high affinity-binding and antagonistic properties are retained after conjugation with a chelator [e.g., 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)] and 111 In-complexation.…”

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confidence: 99%

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Radiolabeled somatostatin receptor antagonists are preferable to agonists forin vivopeptide receptor targeting of tumors

Ginj

Zhang

Waser

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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451

370

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antagonist radioligands ͉ tumor targeting ͉ peptide hormones ͉ neuropeptides ͉ receptor internalization P eptide receptor targeting in vivo is a successful method to image and treat various types of cancers (1). The best example is somatostatin receptor targeting with 111 In-, 90 Y-, or 177 Lu-labeled somatostatin radioligands that are injected into the patients intravenously and accumulate in their somatostatin receptor-expressing tumors. For this purpose, agonists have been selected. The rationale is that agonists, after high-affinity binding to the receptor, usually trigger internalization of the ligandreceptor complex (2). This process of internalization is the basis for an efficient accumulation of the radioligand in a cell over time (1,(3)(4)(5), and it has been considered a crucial step in the process of in vivo receptor targeting with radiolabeled peptides (4-6). Recently, a highly significant correlation between the rate of ligand internalization in vitro into AR42J cells expressing somatostatin receptor subtype 2 (sst 2 ) and the in vivo uptake in the sst 2 -expressing rat tumor model has been reported

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Radiolabeled somatostatin receptor antagonists are preferable to agonists forin vivopeptide receptor targeting of tumors

Ginj

Zhang

Waser

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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451

370

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“…1) have also been characterized in vivo [49]. Later, selective antagonists of sst 1 [50], sst 2 [51], and sst 3 [52] were also developed, which can be useful experimental tools, although the latter two are peptide derivatives. Sst 2 -sst 4 all participate in the mediation of the anticonvulsant action of somatostatin although with some species-dependence regarding sst 2 in particular, which appears to have an anti-epileptic action in rats but not in mice [53].…”

Section: Somatostatinmentioning

confidence: 99%

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Dobolyi¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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Neuropeptides are signaling molecules participating in the modulation of synaptic transmission. Neuropeptides are stored in dense core synaptic vesicles, the release of which requires profound excitation. Only in the extracellular space, neuropeptides act on G-protein coupled receptors to exert a relatively slow action both pre-and postsynaptically. Consequently, neuropeptide modulators are ideal candidates to influence epileptic tissue overexcited during seizures. Indeed, a number of neuropeptides have been implicated in epilepsy and many of them are considered to have endogenous neuroprotective actions. Neuropeptides, present in the hippocampus, the most frequent focus of seizures in temporal lobe epilepsy, received the largest attention as potential anti-epileptic substances. Hippocampal neuropeptides, somatostatin, neuropeptide Y, galanin, dynorphin, enkephalin, substance P, cholecystokinin, vasoactive intestinal polypeptide, and some neuropeptides, which are also hormones such as ghrelin, angiotensins, corticotropin-releasing hormone, adrenocorticotropin, thyrotropin-releasing hormone, oxytocin and vasopressin involved in epilepsy are discussed in the review article. Oral application of neuropeptides as drugs is typically not efficient because of low bioavailability: rapid degradation and insufficient penetration through the blood-brain barrier. Recent progress in the development of non-peptide agonists and antagonists of neuropeptide receptors as well as gene therapeutic approaches leading to the local production of neuropeptides within the central nervous system will also be discussed.

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“…The cloning of the receptors promoted the development of specific SRIF ligands, agonists and antagonists (Rohrer et al, 1998;Bass et al, 1996;Reubi et al, 2000;Hoyer et al, 2004;Tulipano et al, 2002), specific antibodies and genetically modified mice (Kreienkamp et al, 1999;Viollet et al, 2000;Allen et al, 2003;Strowski et al, 2003) An extensive number of studies and a number of reviews Patel 1999;Tannenbaum and Epelbaum, 2000;Csaba and Dournaud, 2001;Olias et al, 2004) have addressed the intracellular signalling pathways responsible for SRIF's diverse actions. The results obtained were mostly from studies performed in cell lines transfected with the recombinant receptors, but also in native systems.…”

Section: Introductionmentioning

confidence: 99%

Novel signals mediating the functions of somatostatin: The emerging role of NO/cGMP

Thermos

2008

Molecular and Cellular Endocrinology

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The neuropeptide somatostatin is a cyclic tetradecapeptide, which is widely distributed in the peripheral and central nervous system. It mediates a plethora of physiological actions and functions as a neurotransmitter, neuromodulator or trophic factor. Somatostatin activates six receptor subtypes that are expressed differentially in different tissues and are coupled to diverse signalling pathways. In order to elucidate the functional role of the individual receptor subtypes, many investigations focused on the assignment of each receptor to a particular signalling pathway.Signalling pathways involving enzyme (adenylate cyclase, phospholipases, phosphatases) and ion channel systems in native and recombinant receptor systems have been extensively studied. A one to one situation (receptor/pathway) has yet to be established, thus justifying the diverse actions of somatostatin. Recently, a NO/cGMP pathway has been shown to mediate the functions of somatostatin and its receptors. This review will present the findings that support the emerging role of NO/cGMP as a novel signal in SRIF's actions in retinal physiology and somatotroph release.

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SST3-selective potent peptidic somatostatin receptor antagonists

Cited by 92 publications

References 47 publications

Radiolabeled somatostatin receptor antagonists are preferable to agonists forin vivopeptide receptor targeting of tumors

Radiolabeled somatostatin receptor antagonists are preferable to agonists forin vivopeptide receptor targeting of tumors

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Novel signals mediating the functions of somatostatin: The emerging role of NO/cGMP

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