Somatostatin receptor subtypes in human immune cells.

Somatostatin is a neuropeptide hormone that is widely distributed throughout the body. It was first discovered as a factor inhibiting the release of growth hormone. Later it was shown to have many functions in the endocrine system including the inhibition of secretion of other pituitary hormones, in addition to that of gastrointestinal hormones. Moreover, somatostatin acts as a neurotransmitter in the nervous system where it also has generally inhibitory effects. Moreover, somatostatin receptors (ssts) are detected in the immune system, although the exact role of somatostatin in the immune system remains elusive. A first step towards a better understanding of the role of somatostatin in the human immune system is to determine which cells express somatostatin and its receptors. Somatostatin exerts its effects through binding to a family of five specific receptors, named sst1 to sst5. The human genes for these receptors were cloned in 1992 and 1993 (1±4). The genes do not have introns. However, for sst2 a spliced mRNA variant has been identified (5, 6) and is named sst2B, whereas the unspliced variant is designated sst2A. After ligand binding the ssts transduce their actions into the cell via coupling to G-proteins (7). Somatostatin is secreted in two biologically active forms: a 14 amino acid peptide (somatostatin-14) and a 28 amino acid peptide (somatostatin-28). Both forms bind with high affinity to all five receptor subtypes. The widely used synthetic analogue, octreotide, binds with high affinity only to sst subtypes 2 and 5 and with lower affinity to receptor subtype 3; binding to receptor subtypes 1 and 4 is undetectable (8, 9). sst have been demonstrated in both rodent and human immune cells (10, 11). In this paper, some of the recent novel insights in the expression and functional significance of ssts in human immune cells are discussed.