Disease relevance of SSTR5

• However, new SSTR5-selective analogues suppressed in vitro PRL secretion (30-40%; P < 0.05) in four of six prolactinomas [1].
• In two cases of glucagonoma and its metastatic lymph nodes in one case, all the SSTR subtype mRNAs except SSTR5 mRNA were expressed [2].
• The regulation of PRL release from cultured adenomas appears to be primarily mediated by SSTR5 [3].
• SSTR5 mRNA was not expressed in four human pituitary tumors (somatotroph adenoma, prolactinoma, and chromophobe adenomas) or in a human insulinoma [4].
• Northern blot analysis of SSTR5 mRNA revealed a 2.4-kilobase transcript in normal rat pituitary and GH3 rat pituitary tumor cells and a 4.0-kilobase transcript in normal human pituitary [4].

Psychiatry related information on SSTR5

• Novel polymorphisms in the somatostatin receptor 5 (SSTR5) gene associated with bipolar affective disorder [5].

High impact information on SSTR5

• Selective nonpeptide agonists with nanomolar affinity have been developed for four of the subtypes (SSTR1, 2, 3, and 4) and putative peptide antagonists for SSTR2 and SSTR5 have been identified [6].
• Analogue affinities determined by membrane radioligand binding in cells stably expressing human SSTR forms were either SSTR2 or SSTR5-selective [1].
• An SSTR5-specific analog also exclusively inhibited GH in acromegalic tumor cells [7].
• Luteinizing hormone was modestly decreased (15-20%) by SSTR2- or SSTR5-specific analogs [7].
• In addition, in SSTR5-expressing cells, RC-160 inhibited CCK-stimulated intracellular calcium mobilization at doses (EC50, 0.35 nM) similar to those necessary to inhibit somatostatin-14 binding (IC50, 21 nM) and CCK-induced cell proliferation (EC50, 1.1 nM) [8].

Chemical compound and disease context of SSTR5

• GH sensitivity to octreotide was not significantly different between SSTR5 mRNA positive and negative adenomas [9].
• 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 [10].
• We investigated the effects of SST-14, lanreotide, and SSTR 2 (BIM-23190) and SSTR 5 (BIM-23268) specific analogs in 18 somatotroph pituitary adenomas in primary culture [11].

Biological context of SSTR5

• Whereas growth inhibition has been reported to follow stimulation of protein tyrosine phosphatase via SSTR2 or inhibition of Ca2+ channels via SSTR5 in heterologous expression systems, the subtype selectivity for signaling apoptosis has not been investigated [12].
• Swapping the C-tail of hSSTR1 with that of hSSTR5 induced internalization (27%) but not up-regulation [13].
• C-terminal region of human somatostatin receptor 5 is required for induction of Rb and G1 cell cycle arrest [14].
• Using a combination of polymerase chain reaction and genomic library screening we have cloned a human gene for a subtype of the somatostatin (SST) receptor (SSTR) termed human SSTR5 (hSSTR5), which is located on chromosome 16 [4].
• In this study we systematically screened the promoter and coding region of the SSTR5 gene for genetic variation that could contribute to the development of neuropsychiatric disorders [5].

Anatomical context of SSTR5

• Most thyroid cancer cell line monolayers and xenografts expressed SSTR3 and SSTR5 mRNAs [15].
• SSTR5 mRNA is detectable in the pituitary and spinal cord by 14-16 weeks of fetal life [16].
• SSTR5 was selectively expressed in activated normal T-cells [17].
• Striated muscle fibres showed an intense positive expression of SSTR1-4, but a weak or negative expression of SSTR5 [18].
• In all cases, the dendritic cells, found mostly in the papillary and upper reticular dermis, showed a strong expression of SSTR1-4, but a weak expression of SSTR5 [18].

Associations of SSTR5 with chemical compounds

• Glucose-stimulated insulin secretion in human islets incubated for 1 hr at 20 mM glucose, and in islets cultured for 24 hr at a near-physiological (6.1 mM) glucose concentration, was inhibited (<50% of the control) by SSTR5-specific analogs and by SS14 and SS28 [19].
• Octreotide binds with greatest affinity to SSTR2 and SSTR5 [20].
• The expression of SSTR2 and/or SSTR5 was 100%, consistent with the presence of RC-160 binding [21].
• Moreover, the somatostatinergic system interacts with the dopaminergic system, which has been hypothesized to be involved in the etiology of autism; in particular, somatostatin secretion is regulated by dopamine, and the dopamine D2 receptor and the SSTR5 receptor interact to form a receptor complex with enhanced functional activity [22].
• This suggests that the inositol phospholipid/calcium pathway could be involved in the antiproliferative effect of RC-160 mediated by SSTR5 in these cells [8].

Physical interactions of SSTR5

• In contrast, SSTR5 bound very few SRIF analogues with high affinity [23].
• The multi-domain protein PIST (protein interacting specifically with Tc10) interacts with the SSTR5 (somatostatin receptor 5) and is responsible for its intracellular localization [24].

Regulatory relationships of SSTR5

• Only SSTR5-selective analogs suppress in vitro PRL secretion from cultured prolactinomas [25].
• SS14, SS28, and different SSTR5 preferential analogs also inhibited islet amyloid polypeptide release during the 24-hr culture [19].
• Nevertheless, SRIF stimulated AC even in the presence of forskolin at higher doses of SRIF in PTX-treated hSSTR5-expressing cells [26].
• Here, we show that PIST is expressed in pancreatic beta-cells and interacts with SSTR5 in these cells [24].
• The aim of this work was to evaluate whether SRIH, SSTR2 and SSTR5-selective agonists influence calcitonin (CT) secretion and gene expression in the TT cell line [27].

Other interactions of SSTR5

• Although hSSTR5 displays approximately 75% sequence identity with rat SSTR5, the two receptors display significantly different pharmacological profiles, especially with respect to their binding affinities for the SST analogue SMS 201-995 [4].
• SSTR3, SSTR4, and SSTR5 mRNA was also dramatically increased at 24 and 48 hr [28].
• Heterologous analogue combinations containing both SSTR2- and SSTR5-selective compounds were more potent in decreasing GH than analogues used alone (P < 0.05), or than combinations of compounds specific for the same receptor subtype (P < 0.005) [1].
• Recent evidence shows that the dopamine D2 receptor (DRD2) and SSTR5 interact physically to form heterodimers with enhanced functional activity [5].
• In the presence of S-Ab, infusion of the SSTR5 agonist had no significant effect on insulin or IAPP secretion [29].

Analytical, diagnostic and therapeutic context of SSTR5

• In situ hybridization of the rat pituitary showed that SSTR5 mRNA is selectively localized in the anterior lobe [4].
• RT-PCR analysis revealed a consistent pattern of SSTR2 and SSTR5 mRNA expression [30].
• Moreover, using immunocytochemistry, blood vessels exhibited receptor-specific localization for SSTR2 and SSTR5 [31].
• Molecular cloning, functional characterization, and chromosomal localization of a human somatostatin receptor (somatostatin receptor type 5) with preferential affinity for somatostatin-28 [4].
• PCR products of SSTR2 and SSTR5 DNA from tumours resistant to somatostatin analogues were directly sequenced [32].

References