Versatile Functions of Somatostatin and Somatostatin Receptors in the Gastrointestinal System

Abstract

Somatostatin (SST) and somatostatin receptors (SSTRs) play an important role in the brain and gastrointestinal (GI) system. SST is produced in various organs and cells, and the inhibitory function of somatostatin-containing cells is involved in a range of physiological functions and pathological modifications. The GI system is the largest endocrine organ for digestion and absorption, SST-endocrine cells and neurons in the GI system are a critical effecter to maintain homeostasis via SSTRs 1-5 and co-receptors, while SST-SSTRs are involved in chemo-sensory, mucus, and hormone secretion, motility, inflammation response, itch, and pain via the autocrine, paracrine, endocrine, and exoendocrine pathways. It is also a power inhibitor for tumor cell proliferation, severe inflammation, and post-operation complications, and is a first-line anti-cancer drug in clinical practice. This mini review focuses on the current function of producing SST endocrine cells and local neurons SST-SSTRs in the GI system, discusses new development prognostic markers, phosphate-specific antibodies, and molecular imaging emerging in diagnostics and therapy, and summarizes the mechanism of the SST family in basic research and clinical practice. Understanding of endocrines and neuroendocrines in SST-SSTRs in GI will provide an insight into advanced medicine in basic and clinical research.

Somatostatin and Its Receptor System in Colorectal Cancer

“…In the GI tract, the majority of SST production occurs in mucosa (>90%), mostly of the stomach, the duodenum, and the jejunum, with <10% taking place in the submucosal and muscle layers. In the mucosa, SST is localized in epithelial endocrine cells/enteroendocrine cells (EECs) [ 24 , 29 , 30 , 36 , 38 , 39 , 40 , 41 ]. The most abundant sources of SST in the GI tract are intestinal EECs, termed δ- or D cells in the antral and the fundic mucosa of the stomach.…”

“…Furthermore, the SRIF system is characterized by a strong antiproliferative activity, increasing cell apoptosis and inhibiting angiogenesis in most of the cancerous tissues [ 12 , 16 , 17 , 18 , 19 , 20 ]. This property is already used in clinical practice [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. SST acts through the activation of five membrane receptors (SSTRs/SSTs), belonging to the G protein-coupled receptor (GPCR) family [ 12 , 16 , 19 , 24 , 27 , 28 ].…”

“…This property is already used in clinical practice [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. SST acts through the activation of five membrane receptors (SSTRs/SSTs), belonging to the G protein-coupled receptor (GPCR) family [ 12 , 16 , 19 , 24 , 27 , 28 ].…”

“…The most abundant source of SST in the GI tract is a group of highly specialized intestinal endocrine cells, known as enteroendocrine cells (EECs) restricted to the mucosa, termed D cells in the stomach [ 29 , 30 , 31 , 32 , 33 ], as well as delta (δ) cells in Langerhans islets of the pancreas [ 34 , 35 , 36 , 37 ]. SST in the GI tract is also produced by neurons of the enteric nervous system (ENS) [ 24 , 29 , 30 , 36 , 38 , 39 , 40 , 41 ]. However, the majority of the circulating SST is secreted by gastrointestinal D cells (~65%), ~30% by the CNS, and ~5% by pancreatic D (δ) cells [ 37 ].…”

“…SST is a peptide that assumes two forms (SST-14 and SST-28), secreted mostly in a paracrine/neurocrine fashion, released in a pulse manner as a very short-lived peptide of about 3 min bioactive half-life in circulation, where it is degraded rapidly by ubiquitous peptidases [ 12 , 22 , 24 , 37 ]. In CNS, the peripheral nervous system (PNS) and pancreas SST-14 is the dominating form, while SST-28 is secreted by D cells in the GI tract [ 42 ].…”