Molecular biology of somatostatin receptor subtypes

Patel, Yogesh C.; Greenwood, Michael T.; Panetta, Rosemarie; Hukovic, Nedim; Grigorakis, Stellios; Robertson, Lauri-Ann; Srikant, Coimbatore B.

doi:10.1016/s0026-0495(96)90076-1

Cited by 104 publications

(42 citation statements)

References 21 publications

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“…More recently, somatostatin binding sites have been classified with respect to receptor subtype. Five subtypes of somatostatin receptor, SSTR-1 to SSTR-5, have been cloned and functionally characterized (84)(85)(86)(87)(88). They all bind somatostatin-14 and somatostatin-28 with similar affinity but show major differences in their affinities for various somatostatin analogs (77).…”

Section: Cytotoxic Analogs Of Somatostatinmentioning

confidence: 99%

Cancer chemotherapy based on targeting of cytotoxic peptide conjugates to their receptors on tumors

Schally

Nagy²

1999

European Journal of Endocrinology

266

228

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In view of non-specific toxicity of most chemotherapeutic agents against normal cells, the development of targeted chemotherapy is warranted. Efficient targeting of chemotherapeutic drugs to the cancerous area could be of great benefit for patients with advanced or metastatic tumors. Targeted cytotoxic peptide conjugates are hybrid molecules composed of a peptide carrier which binds to receptors on tumors and a cytotoxic moiety. New cytotoxic analogs of LHRH, AN-152 in which doxorubicin (DOX) is linked to ]LHRH, and AN-207 which consists of 2-pyrrolino-DOX (AN-201) coupled to the same carrier, show high-affinity binding and are much less toxic and more effective in vivo than their respective radicals in inhibiting tumor growth in LHRH receptor-positive models of human ovarian, mammary, or prostatic cancer. These results suggest that targeted cytotoxic LHRH analogs such as AN-207 could be considered for treatment of these cancers. The presence of receptors for bombesinlike peptides on a wide variety of tumors prompted us to use some of our bombesin/gastrin-releasing peptide antagonists as carrier molecules. Cytotoxic bombesin analogs, such as AN-215 containing AN-201, might find application in the treatment of small cell lung carcinoma (SCLC), and colorectal, gastric, pancreatic, mammary, and prostatic cancers. Since somatostatin receptors are found in various human neoplasms and the receptor subtypes to which octapeptide analogs bind with high affinity have been identified, we synthesized several cytotoxic somatostatin analogs including AN-162 and AN-238 containing DOX and 2-pyrrolino-DOX respectively, linked to octapeptide RC-121. Cytotoxic somatostatin analog AN-238 efficaciously inhibits growth of human breast or prostate cancers expressing somatostatin receptors-2 and -5 and can be used for receptor-targeted chemotherapy. Cytotoxic somatostatin analogs might also find applications for the therapy of human pancreatic, colorectal, and gastric cancer as well as brain tumors and non-SCLC. Cytotoxic compounds linked to analogs of hormonal peptides like LHRH, bombesin, and somatostatin that can be targeted to certain tumors possessing receptors for those peptides could be an important addition to oncological armamentarium.

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Section: Cytotoxic Analogs Of Somatostatinmentioning

confidence: 99%

Cancer chemotherapy based on targeting of cytotoxic peptide conjugates to their receptors on tumors

Schally

Nagy²

1999

European Journal of Endocrinology

266

228

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“…The genes for a family of 5 SRIF receptors have been cloned in recent years. The SRIF receptor genes are all located on different chromosomes, but have a high degree of sequence homology (Patel et al, 1996). CST binds with high affinity to all 5 sst subtypes (Criado et al, 1999;Fukusumi et al, 1997;Siehler et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

The role of cortistatin in the human immune system

Hagen

Dalm

Staal

et al. 2008

Molecular and Cellular Endocrinology

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Please cite this article as: van Hagen, P.M., Dalm, V.A., Staal, F., Hofland, L.J., The Role of Cortistatin in the Human Immune System, Molecular and Cellular Endocrinology (2007Endocrinology ( ), doi:10.1016Endocrinology ( /j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractCortistatin (CST) is a recently described neuropeptide that shares high homology with somatostatin (somatotropin release-inhibiting factor, SRIF) and binds with high affinity to all somatostatin receptor (sst) subtypes. CST is currently known to have a widespread distribution in many human organs including the immune system. The activities specific to CST may be partially attributable to its binding to the growth hormone secretagogue (GHS) receptor (GHS-R) and the orphan Gprotein-coupled receptor MrgX2. Human immune cells produce CST, whereas macrophage lineage and activated endothelium express sst 2 , and human lymphocytes express sst 3 . The human thymus expresses sst 1,2,3 , MrgX2 and almost all immune cells express GHS-R. Moreover, at this very moment promising research with CST in experimental animal models is being performed. On the basis of these promising results, studies aiming to further evaluate the possibilities of CST as a therapeutic agent in human immune mediated inflammatory diseases are warranted.

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“…The aim of the present study was to investigate which SS receptor subtypes were expressed in this cell line. Several authors have previously shown coexistent expression of SS receptor subtype transcripts and suggested simultaneous occurrence of multiple SS receptor subtypes in a single cell [10,11]. Here we provide evidence for multiple SS receptor subtypes in the clonal neuroblastoma cell line LA-N-2 using a combined approach with RT-PCR methodology and competitive radioligand binding with subtype-specific analogues.…”

Section: Introductionmentioning

confidence: 51%

Coexistence of somatostatin receptor subtypes in the human neuroblastoma cell line LA‐N‐2

Nilsson

Folkesson

1997

FEBS Letters

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Five distinct human somatostatin receptor subtypes have recently been cloned and characterized. Previous studies have suggested that these receptor subtypes might display coexistent localization, based on in situ hybridization or immunoblockage experiments. Here we provide evidence for coexistence of somatostatin receptor subtypes 2 and 5 in the human neuroblastoma cell line LA-N-2, using a combined approach with RT-PCR and receptor binding studies with somatostatin analogues. Somatostatin receptor subtypes simultaneously localized to a single cell might serve distinct functions in terms of targeting to different intraneuronal compartments or subtype specificity against so far unidentified somatostatinrelated peptides.

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Molecular biology of somatostatin receptor subtypes

Cited by 104 publications

References 21 publications

Cancer chemotherapy based on targeting of cytotoxic peptide conjugates to their receptors on tumors

Cancer chemotherapy based on targeting of cytotoxic peptide conjugates to their receptors on tumors

The role of cortistatin in the human immune system

Coexistence of somatostatin receptor subtypes in the human neuroblastoma cell line LA‐N‐2

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