Somatostatin GPCR Assays
Background of Somatostatin Receptors
Somatostatin receptors are a group of G protein-coupled receptors with 5 subtypes, activated by their ligands, including endogenous peptides somatostatin-14 (SRIF-14), SRIF-28, cortistatin-17, (CST-17), and numerous synthetic ligands. SRIF-14, and SRIF-28 are the active fragments of precursor somatostatin, released from the hypothalamus. Somatostatin plays a wide range of biological roles in the regulation of multiple hormone releases, including neurotransmitters, growth hormones, thyroid-stimulating hormones, gastrointestinal hormones, pancreatic enzymes, and neuropeptides. In addition, somatostatin is involved in the inhibition of tumor cell proliferation.
Fig.1 Schematic drawing of the molecular interaction of SST and its analogs on G protein inhibitory. (Abdellatif, 2018)
Distributions and Functions of Somatostatin Receptors
Somatostatin receptors are distributed throughout the brain and peripheral tissues. Except for SST4, other subtypes of somatostatin receptors have similar high affinities with SRIF-14 and SRIF-28. The activation of somatostatin receptors stimulates a vast array of intracellular signaling pathways, such as suppression of growth hormone release and regulation of neuronal activity. The agonists of those receptors are the general therapeutics used for the anti-secretion of neuroendocrine tumors.
Subtypes and Mechanisms of Somatostatin Receptors
Somatostatin receptors are a family of G protein-coupled receptors classified into 5 subtypes, including SST1, SST2, SST3, SST4, and SST5 receptors. Somatostatin receptors are found to couple pertussis toxin (PTX)-sensitive G-proteins.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| SST1 receptor | SSTR1 |
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| SST2 receptor | SSTR2 |
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| SST3 receptor | SSTR3 |
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| SST4 receptor | SSTR4 |
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| SST5 receptor | SSTR5 |
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Assay List of Somatostatin Receptors
Creative Biolabs can provide a range of assays of somatostatin receptors. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Somatostatin venom analogs evolved by fish-hunting cone snails: From prey capture behavior to identifying drug leads. |
| Journal | Science advances |
| Published | 2022 |
| Abstract | Somatostatin (SS) is a peptide hormone that plays diverse roles in physiology. Taser-and-tether is one of the most widespread and best-studied fish-hunting strategies. The toxins were demonstrated to exert as biomedical drugs for diagnosing autoimmune disorders, as a fast-acting drug for treating diabetes and studying synaptic transmission, and the calcium channel blocker ω-conotoxin GVIA. The study investigated a deep-water clade of fish-hunting cone snails to find out that predator-prey generated multiple SS analogs, which could be taser-and-tether toxins for therapeutic applications, including pain, cancer, and endocrine disorders. Their findings proved that SS-like peptides were present in animal venoms, which provided a case study for the benefits of merging molecular phylogenetics with behavioral research to accelerate the identification of natural products with medicinal potential. |
| Result |
They observed the extremely slow onset of action of Consomatin Ro1 in mice suggesting that the venom of Asprella snails may contain toxins that target GPCRs expressed in the somatosensory or neuroendocrine systems of prey. Then they performed bioactivity-guided assays with an emphasis on compounds that elicited behavioral changes reminiscent of the slow-onset state of hypoactivity observed in fish after C. neocostatus envenomation. They used the PRESTO-Tango β-arrestin recruitment assay to screen Consomatin Ro1 against a panel of 318 human GPCRs. 10 μM Consomatin Ro1 activated SST4 and, to a lesser extent, SST1.
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Fig.2. Consomatin Ro1 and G1 selectively activate the human SS receptors. (Ramiro, 2022)
References
- Abdellatif, A.; et al. Somatostatin receptors as a new active targeting sites for nanoparticles. Saudi Pharmaceutical Journal. 2018, 26(7): 1051-1059.
- Ramiro, I. B. L.; et al. Somatostatin venom analogs evolved by fish-hunting cone snails: From prey capture behavior to identifying drug leads. Science advances. 2022, 8(12): eabk1410.
