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	SST₁ receptor binds to CST-17, SRIF-14, or SRIF-28 to promote signal transduction SST₁ receptor couples to G_i/G_o protein, activating tyrosine phosphatases (PTPs) and regulating Na⁺/H⁺ exchanger	[¹²⁵I]Tyr¹⁰-CST14 [¹²⁵I]LTT-SRIF-28 [¹²⁵I]Tyr¹¹-SRIF-14 L-797,591 L-817,818 BIM 23052 CH 275 pasireotide	SRA880 BIM 23454
SST₂ receptor	SSTR2	SST₂ receptor binds to CST-17, SRIF-14, or SRIF-28 to promote signal transduction SST₂ receptor couples to G_i/G_o protein, inhibiting adenylyl cyclase SST₂ receptor couples to G_i/G_o protein, activating the potassium channel while inhibiting calcium channel SST₂ receptor couples to G_i/G_o protein in SST₂-transfected CHO cells, activating ERK and PI3K SST₂ receptor inhibits phosphoinositide 3-kinase activity via direct molecular interactions between SST₂ first intracellular loop and the regulatory PI3K p85 subunit or filamin-A	[¹²⁵I]LTT-SRIF-28 [¹²⁵I]Tyr¹⁰-CST14 [¹²⁵I]Tyr3 SMS 201-995 L-054,522 L-779,976 SOM-230 KE 108	[D-Tyr⁸]CYN 154806 BASS antagonist BIM 23627 BIM 23454 DOTA-_JR11
SST₃ receptor	SSTR3	SST₃ receptor binds to CST-17, SRIF-14, or SRIF-28 to promote signal transduction SST₃ receptor couples to G_i/G_o protein, inhibiting adenylyl cyclase	[¹²⁵I]Tyr¹⁰-CST14 [¹²⁵I]LTT-SRIF-28 [¹²⁵I]Tyr⁷-SST₃-ODN-8 BN-81,644 BIM 23030 pasireotide [¹¹¹In]DOTA-BOC-ATE	ACQ090 MK-4256 SST₃-ODN-8
SST₄ receptor	SSTR4	SST₄ receptor binds to CST-17, SRIF-14, or SRIF-28 to promote signal transduction SST₄ receptor couples to G_i/G_o protein, inhibiting adenylyl cyclase SST₄ receptor couples to G_i/G_o protein, activating the potassium channel while inhibiting calcium channel	[¹²⁵I]Tyr¹⁰-CST14 [¹²⁵I]Tyr¹¹-SRIF-14 [¹²⁵I]LTT-SRIF-28 L-803,087 J-2156 veldoreotide	[L-Tyr8]CYN 154806 PRL-2915 BIM 23454
SST₅ receptor	SSTR5	SST₅ receptor binds to CST-17, SRIF-14, or SRIF-28 to promote signal transduction SST₅ receptor couples to G_i/G_o protein, inhibiting adenylyl cyclase and regulating potassium channel and calcium channel	[¹²⁵I]LTT-SRIF-28 [¹²⁵I]Tyr¹⁰-CST14 [¹²⁵I]Tyr¹¹-SRIF-14 L-817,818 BIM 23268 lanreotide pasireotide	S5A1 BIM 23056

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:

SSTR1 SSTR2 SSTR3 SSTR4 SSTR5

Assay No.	Assay Name	Host Cell	Assay Type
Calcium Flux Assay
S01YF-0722-KX188	Magic™ Human SSTR1 In Vitro Calcium Assay, HEK293-Gα15	HEK293-Gα15	Calcium Flux Assay
[³⁵S]GTPγS Binding Assay
S01YF-1122-KX943	Magic™ Human SSTR1 In Vitro [³⁵S]GTPγS binding Assay	CHO-K1	[³⁵S]GTPγS binding Assay

Assay No.	Assay Name	Host Cell	Assay Type
cAMP Assay
S01YF-0722-KX52	Magic™ Human SSTR2 In Vitro Agonist cAMP Assay, HEK293	HEK293	cAMP Assay
S01YF-0722-KX191	Magic™ Rat SSTR2 In Vitro cAMP Assay, CHO-K1	CHO-K1	cAMP Assay
Calcium Flux Assay
S01YF-0722-KX189	Magic™ Human SSTR2 In Vitro Calcium Assay, HEK293-Gα15	HEK293-Gα15	Calcium Flux Assay
S01YF-1122-KX945	Magic™ Human SSTR2 In Vitro Calcium Flux Assay	CHO-K1-Gα16	Calcium Flux Assay
[³⁵S]GTPγS Binding Assay
S01YF-1122-KX947	Magic™ Human SSTR2 In Vitro [³⁵S]GTPγS binding Assay	CHO-K1	[³⁵S]GTPγS binding Assay

Assay No.	Assay Name	Host Cell	Assay Type
Calcium Flux Assay
S01YF-0722-KX192	Magic™ Human SSTR3 In Vitro Calcium Assay, HEK293-Gα15	HEK293-Gα15	Calcium Flux Assay
S01YF-1122-KX949	Magic™ Human SSTR3 In Vitro Calcium Flux Assay	CHO-K1-Gα16	Calcium Flux Assay
[³⁵S]GTPγS Binding Assay
S01YF-1122-KX951	Magic™ Human SSTR3 In Vitro [³⁵S]GTPγS binding Assay	CHO-K1	[³⁵S]GTPγS binding Assay

Assay No.	Assay Name	Host Cell	Assay Type
cAMP Assay
S01YF-0722-KX53	Magic™ Human SSTR4 In Vitro Agonist cAMP Assay, HEK293	HEK293	cAMP Assay
S01YF-1122-KX957	Magic™ Rat SSTR4 In Vitro cAMP Assay	CHO-K1	cAMP Assay
Calcium Flux Assay
S01YF-0722-KX194	Magic™ Human SSTR4 In Vitro Calcium Assay, HEK293-Gα15	HEK293-Gα15	Calcium Flux Assay
S01YF-1122-KX953	Magic™ Human SSTR4 In Vitro Calcium Flux Assay	CHO-K1-Gα16	Calcium Flux Assay
[³⁵S]GTPγS Binding Assay
S01YF-1122-KX955	Magic™ Human SSTR4 In Vitro [³⁵S]GTPγS binding Assay	CHO-K1	[³⁵S]GTPγS binding Assay

Assay No.	Assay Name	Host Cell	Assay Type
Calcium Flux Assay
S01YF-0722-KX196	Magic™ Human SSTR5 In Vitro Calcium Assay, HEK293-Gα15	HEK293-Gα15	Calcium Flux Assay
S01YF-1122-KX958	Magic™ Human SSTR5 In Vitro Calcium Flux Assay	CHO-K1-Gα16	Calcium Flux Assay
[³⁵S]GTPγS Binding Assay
S01YF-1122-KX959	Magic™ Human SSTR5 In Vitro [³⁵S]GTPγS binding Assay	CHO-K1	[³⁵S]GTPγS binding Assay

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, and screened Consomatin Ro1 against a panel of 318 human GPCRs. 10 μM Consomatin Ro1 activated SST4 and, to a lesser extent, SST1. 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.

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