Disease relevance of SSTR

• It is hypothesized that the effect of neuropeptide somatostatin (SS-14) on murine colonic cancer is exerted via the subtype of receptor which does not interact with CH-275 and has no or low affinity for octreotide (SSTR 4, 3 or 5?) [1].
• The purpose of this study was to define the presence and abundance of SSTR subtypes in a rat iliac balloon injury model of intimal hyperplasia [2].

High impact information on SSTR

• METHODS: SSTR messenger RNA expression, and SSTR presence was investigated using reverse-transcription polymerase chain reaction, real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemistry [3].
• The aims of this study were to investigate expression of somatostatin receptor subtypes (SSTRs) 1-5 in rat colonic epithelium and to identify which subtype(s) mediate inhibition of adenosine 3', 5'-cyclic monophosphate (cAMP)-activated secretion using SSTR-selective analogues [4].
• These data indicate that the hippocampal functions of somatostatin might be mediated through diverse but selective second messenger systems activated via SSTR4 and reveal an unsuspected coupling of a neuronal SSTR subtype to a mitogenic signaling pathway [5].
• In vivo behavioral studies demonstrate that intraplantar injection of 20.0 but not 2.0 microM octreotide (OCT, SSTR agonist) significantly reduces capsaicin (CAP, a ligand for TRPV1) -induced flinching and lifting/licking behaviors [6].
• Furthermore, blockade of peripheral SSTRs with c-SOM dramatically enhances CAP-induced behaviors and nociceptor activity, demonstrating SSTR-induced tonic inhibitory modulation of TRPV1 [6].

Biological context of SSTR

• METHODS: SSTR expression was determined by reverse-transcription polymerase chain reaction and immunoblotting [4].
• Taken together with SSTR-specific signal transduction systems, this probably explains the diverse physiological actions of somatostatin [7].
• These findings show that SSTR is expressed in skeletal muscle and that SST acting via the SSTR regulates tyrosine phosphorylation and expression of the epsilon subunit of the AChR in the rat skeletal muscle [8].
• Although several studies have examined which SSTR subtypes control gastrointestinal function, effects of somatostatin on pancreatic gene expression are not well defined [9].
• In addition, because somatostatin did not affect intracellular calcium homeostasis, it can be concluded that SSTR actions are independent of carbachol-stimulated calcium signaling [9].

Anatomical context of SSTR

• Therefore, we examined the expression of mRNA for the five recently cloned SSTR subtypes in the pituitary and hypothalamus of FD and STZ diabetic rats [10].
• The pituitary plasma membrane SSTR concentration was reduced over 50% in FD vs. fed animals [10].
• We investigated the possibility that the SST receptor (SSTR) is expressed in skeletal muscle [8].
• Recently, SS and its receptor (SSTR) have been demonstrated in lymphoid tissues and seem to play a regulatory, largely inhibitory, role in immune responses [11].
• Calculated tumor, kidney and bone marrow doses for 66Ga-DOTATOC based on biodistribution data were 178, 109 and 1.2 cGy/MBq, respectively.We conclude that 66Ga labeled DOTATOC can be used for PET diagnosis and quantitative imaging-based dosimetry of SSTR positive tumors [12].

Associations of SSTR with chemical compounds

• SSTR antigens were colocalized in GH positive cells using rhodamine conjugated secondary antibody for SSTRs and FITC-conjugated secondary antibody for GH [13].
• When AR42J cells were exposed to the cholinergic agonist carbachol in the presence of somatostatin or selective SSTR agonists, significant and dose-dependent reductions in agonist-induced levels of mRNA were noted [9].

Regulatory relationships of SSTR

• This in vitro study investigated the anti-secretory potential of a group of novel, non-peptide, somatostatin-receptor agonists that selectively activate specific SSTR subtypes to assess their potential for oral administration [14].

Analytical, diagnostic and therapeutic context of SSTR

• The presence of SSTR subtypes 1, 2, and 3 was confirmed by Western blotting [3].
• With immunohistochemistry, a strong staining of HSCs was obtained for SSTR subtypes 1, 2, and 3 in CCl4-treated rats, but not in normal rat liver [3].
• CONCLUSION: The high SSTR-binding affinity and high receptor-specific and saturable in vivo tumor uptake indicate that 99mTc-P587 and 99mTc-P829 are promising radiotracers for the clinical detection of SSTR-expressing tumors and other tissues by 99mTc gamma scintigraphy [15].
• By RT-PCR, it was found that AR42J expresses all of the five subtypes of the somatostatin (SST) receptor (SSTR) family, except SSTR4 [16].

References