From the Guidelines
Somatostatin acts primarily by binding to five distinct G protein-coupled receptors (SSTR1-5) on target cells, inhibiting numerous physiological processes throughout the body, including cell proliferation, hormone secretion, and gastrointestinal motility. Upon receptor binding, somatostatin activates inhibitory G proteins that decrease intracellular cyclic AMP and calcium levels while increasing potassium conductance, leading to hyperpolarization of cell membranes and reduced secretory activity 1.
Mechanisms of Action
- In the gastrointestinal tract, somatostatin inhibits the release of numerous hormones including gastrin, cholecystokinin, secretin, and vasoactive intestinal peptide, resulting in decreased gastric acid production, reduced pancreatic enzyme secretion, and slowed GI motility.
- In the pancreas, it suppresses both insulin and glucagon release from islet cells.
- Somatostatin also inhibits growth hormone and thyroid-stimulating hormone release from the anterior pituitary.
- Additionally, it reduces splanchnic blood flow and inhibits cell proliferation in various tissues, which is why synthetic somatostatin analogs like octreotide and lanreotide are effective in treating conditions characterized by hormone hypersecretion, such as acromegaly, carcinoid syndrome, and certain neuroendocrine tumors, as shown in the CLARINET study 1.
Clinical Applications
- The inhibitory effects on secretion and motility also make somatostatin useful in managing variceal bleeding and pancreatic fistulas.
- The use of somatostatin analogs, such as octreotide and lanreotide, is recommended for tumor growth control in advanced SSTR-positive, slowly-growing GI and Pan-NETs up to a Ki-67 of 10% 1, with a European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) v1.1 score of 3 for lanreotide and 2 for octreotide.
From the FDA Drug Label
The mechanism of action of lanreotide is believed to be similar to that of natural somatostatin. Lanreotide has a high affinity for human somatostatin receptors (SSTR) 2 and 5 and a reduced binding affinity for human SSTR1, 3, and 4. Activity at human SSTR2 and 5 is the primary mechanism believed responsible for GH inhibition. Like somatostatin, lanreotide is an inhibitor of various endocrine, neuroendocrine, exocrine, and paracrine functions
The mechanisms of action of Somatostatin (SST), as inferred from lanreotide, include:
- Inhibition of GH secretion through high affinity binding to human somatostatin receptors (SSTR) 2 and 5
- Inhibition of various endocrine, neuroendocrine, exocrine, and paracrine functions
- Reduction of IGF-1 levels
- Inhibition of basal secretion of motilin, gastric inhibitory peptide, and pancreatic polypeptide
- Inhibition of postprandial secretion of pancreatic polypeptide, gastrin, and cholecystokinin (CCK)
- Reduction and delay in postprandial insulin secretion
- Inhibition of meal-stimulated pancreatic secretions
- Reduction of duodenal bicarbonate and amylase concentrations
- Transient reduction in gastric acidity
- Inhibition of gallbladder contractility and bile secretion
- Inhibition of meal-induced increases in superior mesenteric artery and portal venous blood flow
- Transient decrease in glomerular filtration rate (GFR) and filtration fraction 2
From the Research
Mechanisms of Action of Somatostatin (SST)
The mechanisms of action of Somatostatin (SST) are mediated by specific membrane-bound receptors present in all somatostatin target tissues, such as brain, pituitary, pancreas, and gastrointestinal tract 3, 4. The key aspects of SST's mechanisms of action include:
- Inhibition of endocrine and exocrine secretions 5
- Modulation of neurotransmission, motor and cognitive functions 5
- Inhibition of intestinal motility, absorption of nutrients and ions, and vascular contractility 5
- Control of the proliferation of normal and tumor cells 5
- Blockade of autocrine/paracrine growth-promoting hormone and growth factor production 5
- Inhibition of growth factor-mediated mitogenic signals and induction of apoptosis 5
- Inhibition of growth-promoting hormone and growth factor secretion, and antiangiogenic actions 5
Somatostatin Receptors
Somatostatin receptors are expressed in various tissues, including:
- Gastrointestinal mucosa 3, 4
- Peripheral nervous system 3, 4
- Gut-associated lymphoid tissue 3, 4
- Neuroendocrine tumors of the gastrointestinal tract 3, 4, 6
- Pituitary gland 7
- Brain 5
- Pancreas 5
- Adrenals 5
- Thyroid 5
- Kidney 5
- Immune system 5
Subtypes of Somatostatin Receptors
There are five subtypes of somatostatin receptors (SSTR1-SSTR5) that are widely distributed in normal and cancer cells 5. SSTR2 is the most frequently and abundantly expressed subtype in many neuroendocrine tumors 4, 5. The expression of somatostatin receptors in tumors can be used to predict the therapeutic efficacy of somatostatin analogs, such as octreotide 3, 4, 6.