Functional role of somatostatin receptors in neuroendocrine and immune cells

Somatostatin is a neuropeptide that is widely distributed throughout the body. It was first identified as a growth hormone release‐inhibiting factor synthesized in the hypothalamus. Outside the central nervous system (CNS), the peptide is present in endocrine as well as non‐endocrine tissues. Somatostatin functions as a peptide with a generally inhibitory action in the CNS and endocrine system. In the CNS, it can act as a neurotransmitter, while in peripheral tissues, it regulates endocrine and exocrine secretion and acts as a modulator of motor activity in the gastrointestinal tract. Besides these actions, somatostatin has also been shown to have antiproliferative effects in vitro . Somatostatin binds to five different subtype receptors (sst) which are differently expressed by various tissues. These receptors have been described also in the immune system of various species including humans. It is therefore a long known fact that human immune cells and their progenitors can express somatostatin receptors. As a consequence, ssts were described in primary and secondary human immune organs. Somatostatin produced by immune cells may act as an autocrine or paracrine regulator within the local immune microenvironment in mice. The synthesis, however, of somatostatin has not been demonstrated in human immune cells. In a recent study, the expression of another somatostatin‐like peptide; cortistatin‐17 (CST) was found in human lymphoid tissues, immune cells and lymphoid cell lines. On the basis of these observations, a role for CST as an endogenous ligand for sst in the human immune system, rather than SS itself was hypothesized. Somatostatin receptor expression can be detected in vivo somatostatin receptor scintigraphy after injection of 111 In‐labelled octreotide, a somatostatin analogue. This technique is used extensively for the localization of neuroendocrine tumours and other malignancies that express high levels of sst. Among the non‐neuroendocrine tumours that can be visualized by octreotide scintigraphy are malignant lymphomas, both T and B non‐Hodgkin's lymphomas and Hodgkin's disease lymphomas. In a number of infectious diseases (e.g. tuberculosis), autoimmune diseases (e.g. Graves' ophthalmopathy) and other immune‐mediated diseases (e.g. sarcoidosis and rheumatoid arthritis), the sites of inflammation can also be visualized. Based on the receptor pattern in autoimmune diseases, controlled studies are warranted to investigate the efficacy of somatostatin analogues in the treatment of autoimmune diseases like rheumatoid arthritis. In rheumatoid arthritis, not only immune cells can be targeted by these analogues but also synoviocytes and synovial blood vessels. Moreover, receptor expression during treatment in such diseases can be monitored by octreotide scintigraphy.