Disease relevance of SSTR4

• In a carcinoid, SSTR1 and SSTR4 mRNAs were detected [1].
• High affinity agonist binding to hSSTR4 was significantly reduced by GTP and pertussis toxin, indicating association of the expressed receptor with pertussis toxin-sensitive guanine nucleotide-binding proteins [2].
• SSTR4 mRNA was faintly positive in only one anaplastic carcinoma xenograft [3].
• It is noteworthy that SSTR4 and 5 were strongly expressed in the epidermis of psoriasis patients, but weakly expressed in the epidermis of those with atopic dermatitis and normal skin [4].
• SSTR3 and SSTR4 mRNAs were detected in 1 and 2 cases of somatotroph adenoma, respectively [5].

High impact information on SSTR4

• Some of the subtypes are also coupled to inward rectifying K(+) channels (SSTR2, 3, 4, 5), to voltage-dependent Ca(2+) channels (SSTR1, 2), a Na(+)/H(+) exchanger (SSTR1), AMPA/kainate glutamate channels (SSTR1, 2), phospholipase C (SSTR2, 5), and phospholipase A(2) (SSTR4) [6].
• Surprisingly, several well-characterized synthetic somatostatin analogs fail to exhibit high-affinity binding to hSSTR4, indicating the existence of pharmacologically different receptor subtypes [7].
• SSTR3 was detected in occasional alpha-cells, and SSTR4 was absent [8].
• SSTR3 messenger RNA was undetectable in normal and cancer EC, whereas SSTR4 and SSTR5 were present in both cell types [9].
• SSTR4 expression was also undetectable in 11 GH-secreting tumors, 3 prolactinomas, and 1 ACTH-secreting tumor tested [10].

Chemical compound and disease context of SSTR4

• METHODS: Nonradioactive in situ hybridization was performed with specific fluorescein-labeled SSTR2 and SSTR4 riboprobes on consecutive sections of benign prostatic hyperplasia (BPH) and prostate cancer tissues [11].

Biological context of SSTR4

• The SSTR4 gene maps to human chromosome 20 [2].
• Cloning and expression of a human somatostatin-14-selective receptor variant (somatostatin receptor 4) located on chromosome 20 [2].
• A human genomic library was screened with a 1.2 kb fragment of rSSTR4 containing the full open reading frame and a genomic clone, hSSTR4, was isolated [12].
• Based on the deduced amino acid sequence, this gene encodes a 418 amino acid protein displaying sequence similarity, particularly within putative transmembrane domains, with the recently cloned human SSTR1 (62%), SSTR2 (64%) and SSTR4 (58%) receptors [13].
• The nucleotide sequences of the SSTR3 and SSTR4 genes in COR-L103 cells were normal [14].

Anatomical context of SSTR4

• Northern blot analysis revealed the presence of an SSTR4 mRNA species of approximately 4 kilobases in select regions of the monkey brain, including the hippocampus, hypothalamus, cortex, and striatum, with little or no receptor mRNA detected in either the olfactory tubercle, medulla, cerebellum, or amygdala [2].
• Membranes prepared from COS-7 cells transiently expressing the hSSTR4 gene bound 125I-[Leu8,D-Trp22,Tyr25]SST-28 in a saturable manner with high affinity (approximately 60 pM) and with a pharmacological profile and rank order of potency ([D-Trp8]SST-14 > SST-14 > SMS 201-995 > SST-28 > MK-678) indicative of a SST-14-selective receptor [2].
• SSTR4 is expressed in fetal brain, hypothalamus and spinal cord but not pituitary [15].
• In summary, the present study clearly demonstrates the presence of hSSTR1-3 in tumoral and nontumoral epithelial cells as well as in the stromal compartment, whereas hSSTR4 was found to be confined to epithelial cells, and SSTR5 was not detectable [16].
• SSTR3 was present in intracellular granules, while SSTR4 and SSTR5 were expressed on the lumenal membranes of the tubules [17].

Associations of SSTR4 with chemical compounds

• The anti-inflammatory action of TT-232 is mediated through the SSTR4 receptor, and its antitumor activity is mediated through the SSTR1 receptor and by the tumor-specific isoform of pyruvate kinase [18].
• We conclude that cisplatin neuropathy is accompanied by an increase in plasma somatostatin immunoreactivity with an increase in SSTR4 expression in rats [19].
• Compound 19 bound hSSTR4 with a Ki of 100 nM [20].
• The rank of the potency of the analogues are: somatostatin-14 = somatostatin-28 >> RC-160 >> SMS201-995 for the hSSTR4 and somatostatin-28 > somatostatin-14 >> RC-160 > SMS201-995 for the hSSTR5 [21].

Other interactions of SSTR4

• AD cortex showed a marked reduction in neuronal expression of SSTR4 and 5 and a modest decrease in SSTR2-like immunoreactivity without any changes in SSTR1 immunoreactive neurons [22].
• SSTR4 and SSTR5 transcripts were only rarely detected [23].
• A potential role of somatostatin and its receptor SSTR4 in the migration of hepatic oval cells [24].

Analytical, diagnostic and therapeutic context of SSTR4

• Molecular cloning and sequencing of a human somatostatin receptor, hSSTR4 [12].
• METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed followed by Southern blotting on mouse kidney RNA for SSTR3, SSTR4, and SSTR5 [17].
• Western blot assay and immunohistochemical staining confirmed the expression of SSTR4 by HOCs [24].
• RT-PCR and quantitative real-time PCR showed that SSTR4 was preferentially expressed by HOCs [24].

References