Somatostatin Family Related Drug Discovery Products
Creative Biolabs has the assays you can rely on for high throughput screening, lead optimization, characterizing and discovering targets, and uncovering the complexity of disease pathways. We can offer membrane protein in vitro assay kits that save valuable laboratory time and is ideal for high throughput screening.
Creative Biolabs offers high-quality, innovative tools to help research groups accelerate membrane protein drug discovery. They can be found by targets. If there is no product that meets your needs, please contact us.
A naturally occurring inhibitory polypeptide hormone called somatostatin was initially discovered in the hypothalamus of sheep. It is widely dispersed in peripheral tissues as well as the human central nervous system (CNS). A wide range of biological processes are influenced by somatostatin, including the control of neurotransmission and secretion, as well as the inhibition of the production of neuropeptides, thyroid-stimulating hormone (TSH), gastrointestinal (GI) hormones, growth hormone (GH), and pancreatic enzymes. It modifies the rate of smooth muscle contraction, gastric emptying, and intestinal blood flow. Additionally, it prevents the growth of both healthy and malignant cells. Somatostatin has become a significant pharmacological target because of its strong and comprehensive antisecretory effects.
Fig.1. The hormonal actions of somatostatin. (Kumar & Grant, 2010)
Creative Biolabs is a world-leading provider in membrane protein drug discovery and we can offer somatostatin family related drug discovery tools for our clients:
Overview of Somatostatin Family
- SSTR1
SSTR1 inhibits adenylate cyclase by forming a coupling with Gα3 and Gαi1/2. SSTR1 activates the serine/threonine mitogen-activated protein kinase (MAPK) by inducing PTP activity. Usually, the growth factors, cytokines, and hormones that have mitogenic effects are mediated through the MAPK pathway. However, the MAPK pathway can also stop cell growth to encourage cell differentiation, depending on the cell system and extracellular environment. The Ras GTPase's ability to bind GTP is enhanced when the tyrosine kinase domain of growth factor receptors is activated, and this interaction with Sos via unique adaptors triggers the MAPK pathway.
- SSTR2
Since it is the primary receptor-pharmacological target mediating the advantageous effects of the currently used somatostatin analogs, SSTR2 is the best-studied mediator of somatostatin's antiproliferative action. SSTR2 is regarded as a tumor suppressor in pancreatic cancer itself. The ability of SSTR2A and SSTR2B to inhibit adenylate cyclase depends on the G protein subunits present in each kind of cell. Additionally, SSTR2 promotes PLC, which in turn causes Ca2+ mobilization.
- SSTR3
By coupling to Gαi, SSTR3 prevents adenylate cyclase activity in a pertussis toxin-sensitive pathway. Similar to SSTR1 and 2, SSTR3 can also activate a PTP. When SSTR3 is overexpressed, it causes SHP-2 to be triggered, which then causes Raf-1 to become inactive.
- SSTR4
The SSTR family of receptor subtypes, SSTR4, has received the least amount of research. Gi and adenylate cyclase are coupled to SSTR4, which inhibits the synthesis of cAMP. By promoting the formation of arachidonate and phospholipase A (PLA)-2, which are downstream of PI3K, it stimulates PTP activity and turns on MAPK. Because it promotes protein kinase C (PKC) and MAPK-mediated serine phosphorylation of the signal transducer and activator of transcription 3 (STAT3), SSTR4 is the only receptor that, when bound to somatostatin, causes cell proliferation.
- SSTR5
SSTR5 is high affinity to somatostatin-28. Adenylate cyclase is inhibited by SSTR5 through a pertussis toxin-sensitive mechanism. It produces K+, which causes cells to become hyperpolarized. Cell hyperpolarization then causes the L-type voltage-sensitive Ca2+ channels to shut, reducing Ca2+ influx. SSTR5 has an impact on PLC through a mechanism that mostly involves Gaq and only partially Gi. PLC breaks down phosphatidylinositol 4,5-bisphosphate (PIP2) to produce inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). In the cytosol, where it binds to Ca2+ channels and enhances Ca2+ influx.
Fig.2. The main signaling cascades of SSTRs. (Theodoropoulou & Stalla, 2013)
References
- Kumar, U.; Grant, M. Somatostatin and somatostatin receptors. Cellular peptide hormone synthesis and secretory pathways. 2010, 97-120.
- Theodoropoulou, M.; Stalla, G.K. Somatostatin receptors: from signaling to clinical practice. Frontiers in neuroendocrinology. 2013, 34(3): 228-252.
