Disease relevance of Sstr1

• Indeed, the inhibitory effect of the peptide on growth hormone mRNA levels was totally insensitive to pertussis toxin treatment but was totally abolished under conditions which block somatostatin receptor internalization [1].
• This paper extends these observations by defining the somatostatin receptor (SSTR) isoform most likely expressed by granuloma inflammatory lymphocytes [2].
• The mRNA for sst1 was detected in 65% of the ovarian cancer specimens, while the incidence of sst2A, sst3 and sst5 was 65%, 41% and 24%, respectively [3].
• Antitumor effect of in vivo somatostatin receptor subtype 2 gene transfer in primary and metastatic pancreatic cancer models [4].
• S49 mouse lymphoma cells contain a beta-adrenergic receptor coupled to Gs that stimulates adenylyl cyclase and a somatostatin receptor coupled to Gi that inhibits adenylyl cyclase [5].

High impact information on Sstr1

• BACKGROUND & AIMS: Somatostatin receptor subtype 2 (sst2) agonists inhibit gastric secretion [6].
• High basal gastric acid secretion in somatostatin receptor subtype 2 knockout mice [6].
• While trying to identify new members of the somatostatin receptor family of G protein-coupled receptors, we isolated cDNAs from a mouse brain library encoding two related receptor-like proteins, designated msl-1 and msl-2, of 380 and 372 amino acids, respectively [7].
• The PCR and conventional library screening were used to clone the brain-specific somatostatin receptor rSSTR-4 from a rat genomic library [8].
• To assess the contribution of somatostatin receptor subtype 5 (SST5) to somatostatin receptor subtype 2 (SST2) action in these cells, we assessed multipathway responses to novel highly monoreceptor-selective peptide agonists and multireceptor agonists, including octreotide and somatostatin-28 [9].

Chemical compound and disease context of Sstr1

• These data show that pertussis toxin-insensitive activation of the sst1 receptor subtype mediates somatostatin-induced increase in sensitivity to glutamate, whereas decrease in the response to glutamate is linked to pertussis toxin-sensitive activation of the sst2 receptor subtype [10].
• Results from sst1 KO retinas demonstrate that either SRIF or the sst2 receptor preferring agonist octreotide, pertussis toxin-dependently inhibit AC activity [11].

Biological context of Sstr1

• CH-275 at 100 nM (a selective agonist at sst1 receptors) partially inhibited electrical activity but without membrane potential hyperpolarization [12].
• Localization of somatostatin receptor genes on mouse chromosomes 2, 11, 12, 15, and 17: correlation with growth QTLs [13].
• Several Smstr genes map within these regions, suggesting that they be considered candidate genes for these quantitative trait loci [13].
• MicroPET imaging of gene transfer with a somatostatin receptor-based reporter gene and (94m)Tc-Demotate 1 [14].
• We have previously shown that pharmacological doses of thyroid hormone (levothyroxine [LT4]) inhibit growth of murine TtT-97 thyrotropic tumors in association with upregulation of somatostatin receptor type 5 (sst5) mRNA and somatostatin receptor binding [15].

Anatomical context of Sstr1

• Among them, the sst1 receptor has been localised to SRIF-containing amacrine cells in the rat and rabbit retina [16].
• [125I]-Tyr0-DTrp8-SRIF14 binding was not significantly modified in sst1 KO mouse brain with the noticeable exception of the substantia nigra and only moderately decreased in pituitary [17].
• Radioligand binding studies were performed in CCL39 cells expressing the five human recombinant receptors and compared to binding in membranes of rat cerebral cortex with [125I]Tyr11-SRIF14 which in the presence of 120 mM labels primarily sst1 receptor as suggested by the better correlation hsst1 and similar rank order of potency [18].
• In the whole hippocampus of sst1 KO mice, sst2 mRNA, protein and binding are higher than in WT and reverse transcription-polymerase chain reaction of the CA3 subarea confirms an increase of the sst2 messenger [19].
• Activation in vitro of somatostatin receptor subtypes 2, 3, or 4 stimulates protein tyrosine phosphatase activity in membranes from transfected Ras-transformed NIH 3T3 cells: coexpression with catalytically inactive SHP-2 blocks responsiveness [20].

Associations of Sstr1 with chemical compounds

• Mutation of an aspartate at residue 89 in somatostatin receptor subtype 2 prevents Na+ regulation of agonist binding but does not alter receptor-G protein association [21].
• Somatostatin receptor subtypes sst1 and sst2 elicit opposite effects on the response to glutamate of mouse hypothalamic neurones: an electrophysiological and single cell RT-PCR study [10].
• Somatostatin released from capsaicin-sensitive afferents exerts systemic anti-nociceptive actions, presumably via somatostatin receptor subtype 4 (sst4) [22].
• Nevertheless, DOTATOC was clearly superior to the other DOTA-somatostatin analogs tested, as well as OctreoScan, as indicated by the highest tumor-to-nontarget-tissue ratio, including the tumor-to-SSTR-positive-tissue ratios [23].
• Somatostatin receptor subtype 5 regulates insulin secretion and glucose homeostasis [24].

Physical interactions of Sstr1

• We demonstrate that this effect is dependent on the internalization of somatostatin-receptor complexes and that it is totally independent from the peptide-induced inhibition of adenylate cyclase [1].
• Cortistatin radioligand binding in wild-type and somatostatin receptor-deficient mouse brain [25].

Regulatory relationships of Sstr1

• We purified somatostatin receptors by immunoaffinity from pancreatic membranes that strongly expressed the type 2 somatostatin receptor sstr2 [26].

Other interactions of Sstr1

• Smstr1 through Smstr5 were localized to mouse chromosomes 12, 11, 15, 2, and 17, respectively [13].
• In WT mice, SRIF and the sst1 agonist CH-275 reduce epilepsy whereas sst1 blockade with its antagonist SRA-880 increases the bursting discharge [19].
• Role of amphiphysin II in somatostatin receptor trafficking in neuroendocrine cells [27].
• Gi alpha 3 and G(o) alpha selectively associate with the cloned somatostatin receptor subtype SSTR2 [28].
• SSTR2A is the dominant somatostatin receptor subtype expressed by inflammatory cells, is widely expressed and directly regulates T cell IFN-gamma release [29].

Analytical, diagnostic and therapeutic context of Sstr1

• About half of the neurones tested by single cell reverse transcriptase polymerase chain reaction (RT-PCR) expressed only one sst receptor (sst1 in 26% and sst2 in 22% of studied cells) [10].
• Expression of sst1 or sst2 mRNA subtypes matched totally with the effects of somatostatin on sensitivity to glutamate in 79% of the neurones processed for PCR after recordings [10].
• Allelic variation in the five somatostatin receptor genes (Smstr) could contribute to growth rate and overall body size [13].
• Molecular cloning and functional expression of a brain-specific somatostatin receptor [8].
• Somatostatin receptor subtype 2 (SSTR2) has been used as a reporter probe for gamma-camera imaging of gene transfer in animal models [14].

References