Disease relevance of SSTR1

• In a carcinoid, SSTR1 and SSTR4 mRNAs were detected [1].
• In three cases of pheochromocytoma, SSTR1 and SSTR2 mRNAs were detected, showing an expression pattern identical to that of normal adrenal gland [1].
• The effects of GTP gamma S and pertussis toxin on [125I-Tyr11]somatostatin-14 binding indicated that SSTR2 may couple exclusively to pertussis toxin-sensitive G proteins, whereas SSTR1 may couple to both pertussis-sensitive and -insensitive G proteins [2].
• A PCR product of the expected size of 334 bp, corresponding to SSTR1, was expressed only in EC from prostate cancer, whereas the expected 461-bp product of SSTR2 was found only in EC from normal prostate [3].
• The SSTR1 transcript was also highly expressed in prolactinomas (1296 +/- 669 pg/pg GAPDH) [4].

Psychiatry related information on SSTR1

• Expression of somatostatin receptor subtypes (SSTR1-5) in Alzheimer's disease brain: an immunohistochemical analysis [5].
• This mapping of SSTR mRNA expression patterns in human fetal neural tissues is an important first step toward our goal of determining the role of SST in the nervous system during early stages in human development [6].
• Examination of somatostatin receptor binding in Alzheimer's disease and Huntington's disease may improve understanding of the role of somatostatin in both these illnesses [7].
• As neuronal production of somatostatin is involved the idea is striking whether somatostatin-receptor density in the cortex of cerebral hemispheres might be related to gender identity [8].
• CONCLUSION: Somatostatin receptor scintigraphy improves tumor detection, has major clinical significance and should be performed systematically for staging and therapeutic decision making in patients with GEP tumors [9].

High impact information on SSTR1

• Somatostatin receptors expressed on tumor cells form the rationale for somatostatin analog treatment of patients with somatostatin receptor-positive neuroendocrine tumors [10].
• Here, we show that dopamine receptor D2R and somatostatin receptor SSTR5 interact physically through hetero-oligomerization to create a novel receptor with enhanced functional activity [11].
• Somatostatin receptor concentrations were measured in patients with Alzheimer's disease and controls [12].
• Somatostatin receptor expression in primary gastric versus nongastric extranodal B-cell lymphoma of mucosa-associated lymphoid tissue type [13].
• Expression of human somatostatin receptor subtype 3 in pancreatic cancer in vitro and in vivo [14].

Chemical compound and disease context of SSTR1

• These findings suggest that SSTR2 receptors can be regulated and they associate with pertussis toxin-sensitive guanine nucleotide-binding proteins, whereas SSTR1 receptors do not [15].
• Analysis of residual tumors from thyroid hormone-treated mice showed the specific up-regulation of SSTR1 and SSTR5 mRNA subtypes and the appearance of abundant, high affinity SSTR receptor-binding sites within the tumor [16].
• This implies that SST analogs like SMS 201-995, known to interact with SSTR2A, but not with SSTR1, act on pituitary tumors mainly via the SSTR2 subtype [17].
• Accordingly, in the present study, we determined the effects of tamoxifen, a selective estrogen receptor (ER) modulator (SERM), and estradiol on SSTR1 and SSTR2 expression at the mRNA and protein levels in ER-positive and -negative breast cancer cells [18].
• Because melanomas arise from neural crest cells, we sought to evaluate the distribution of SSTR subtypes found in these tumors and their functional significance by imaging with 111In-pentetreotide scintigraphy (OctreoScan) [19].

Biological context of SSTR1

• Both analogues caused an inhibition of cell proliferation at a concentration higher than 10 nM in accordance with their affinities for the SSTR1 receptor subtype [20].
• There is 46% identity and 70% similarity between the amino acid sequences of SSTR1 and SSTR2 [21].
• Binding experiments were performed on crude membranes by using [125I-labeled Tyr11] somatostatin-14; RC-160 exhibited moderate-to-high affinities for SSTR2, -3, and -5 (IC50, 0.17, 0.1 and 21 nM, respectively) and low affinity for SSTR1 and -4 (IC50, 200 and 620 nM, respectively) [22].
• On the other hand, in the nonresponder group, CT secretion was reduced by the SSTR1 selective agonist, whereas cell viability was inhibited by SSTR2 selective agonists [23].
• Highly informative simple tandem repeat DNA polymorphisms were identified in SSTR1 and SSTR2 [24].

Anatomical context of SSTR1

• Binding experiments were performed on membranes from COS-7 cells expressing human SSTR1 or SSTR2 using 125I-labeled [Tyr11]S-14 or [Tyr3]SMS-201-995, respectively [20].
• Effects of the stable somatostatin analogue RC-160 on cell proliferation, tyrosine phosphatase activity, and intracellular calcium concentration were investigated in CHO cells expressing the five somatostatin receptor subtypes SSTR1 to -5 [22].
• RNA blotting studies show that SSTR1 and SSTR2 are expressed at highest levels in jejunum and stomach and in cerebrum and kidney, respectively [21].
• Although there is no absolute specificity of any SSTR for an islet cell type, SSTR1 is beta-cell selective, and SSTR2 is alpha-cell selective [25].
• Double label confocal fluorescence microscopy showed that when SSTR1 and SSTR5 subtypes were coexpressed in Chinese hamster ovary-K1 cells and treated with agonist they underwent internalization and were colocalized in cytoplasmic vesicles [26].

Associations of SSTR1 with chemical compounds

• A single Ser305 to Phe mutation in TM VII increased the affinity of SSTR1 for SMS 201-995 nearly 100-fold [27].
• In SSTR1-expressing cells, only RC-160 induced stimulation of a tyrosine phosphatase activity [20].
• RC-160 had no effect on the basal or carbachol-stimulated calcium concentration in cells expressing SSTR1 to -4 [22].
• We found that stimulation of SSTR1 cells was capable of increasing phosphotyrosine phosphatase activity, despite the coupling of both receptors to the inhibition of adenylyl cyclase in these cells [28].
• Cultured tumor cells were treated with SRIH, lanreotide (BIM-23014), or SRIH analogs selective for SSTR2 (BIM-23120), SSTR5 (BIM-23206), or SSTR1 (BIM-23926) [29].

Physical interactions of SSTR1

• Currently available somatostatin analogs predominantly bind to the somatostatin receptor subtype (SSTR)2 subtype, and control GH and IGF-I secretion in approximately 65% of patients with acromegaly, their efficacy relating to receptor density and subtype expression [30].
• SRIF2 receptors are not efficiently coupled to G proteins and have a distinct but overlapping distribution in brain with SRIF1 receptors [31].
• SPET with 111In-SMS and 123I-IBZM after therapy revealed no change or a possible increase in somatostatin receptor binding potential and a possible decrease in dopamine D2 receptor binding potential [32].
• Gi alpha 1 selectively couples somatostatin receptor subtype 3 to adenylyl cyclase: identification of the functional domains of this alpha subunit necessary for mediating the inhibition by somatostatin of cAMP formation [33].
• CONTEXT: Cortistatin binds all somatostatin receptor subtypes but also has particular central actions; moreover, a specific cortistatin receptor has also been discovered [34].

Regulatory relationships of SSTR1

• SRIF analog affinities were determined by membrane radioligand binding in cells stably expressing the human SSTR forms [35].
• Here we have investigated the molecular basis of hSSTR1 up-regulation. hSSTR1 was up-regulated by SST in a time-, temperature-, and dose-dependent manner to saturable levels, in intact cells but not in membrane preparations [36].
• Bim-23244, a somatostatin receptor subtype 2- and 5-selective analog with enhanced efficacy in suppressing growth hormone (GH) from octreotide-resistant human GH-secreting adenomas [37].
• These data supported the idea of somatostatin receptor subtype-specific control of PRL secretion in such tumors [4].
• In this study, we have determined the somatostatin receptor subtypes expressed in various endocrine tumors using a reverse transcriptase polymerase chain reaction method [1].

Other interactions of SSTR1

• Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine tumors [1].
• We therefore tested SSTR subtype-specific SRIF analogs in primary human fetal pituitary cultures (23-25-wk gestation) to elucidate their role in regulating human pituitary function [35].
• In two cases of glucagonoma and its metastatic lymph nodes in one case, all the SSTR subtype mRNAs except SSTR5 mRNA were expressed [1].
• Of 55 tumors, 12 expressed SSTR1, and 14 expressed SSTR3 mRNA [38].
• OUTCOME MEASURES: GH and prolactin (PRL) medium concentrations were tested by hormone assay, and SSTR mRNA was tested by RT-PCR [39].

Analytical, diagnostic and therapeutic context of SSTR1

• Tyrosine phosphatase was stimulated by both these analogues in SSTR2 and by RC-160 in SSTR1 at affinities similar to their ability to inhibit growth and bind to receptors, implicating tyrosine phosphatase as a transducer of the growth inhibition signal [20].
• This is the first demonstration of the presence of SSTR1, SSTR2, and SSTR3 in primary human tumors using in situ hybridization [38].
• Quantitative RT-PCR showed SSTR1 mRNA mean levels of 6 +/- 2.2 x 10(4) molecules/ microg reverse-transcribed total RNA [40].
• Immunohistochemistry for SSTR1 and SSTR2 was performed on eight pairs of normal human eyes (28-74 years) imbedded in paraffin [41].
• Effects of SSTR agonists on proliferation and apoptosis of tumour cells and HSCs were assessed by the 5-bromo-2' deoxyuridine and TUNEL methods, respectively [42].

References