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Many neuroendocrine gastrointestinal and lung tumors express sst2A somatostatin receptors. Because the cellular location of sst2A in the corresponding non-neoplastic tissue is unknown, we searched for sst2A immuno-reactive cells and characterized their type in these tissues using a highly specific sst2A antibody (R2–88). Epithelial sst2A cells, identified as neuroendocrine, gastrin-producing cells, were found in large numbers in the antrum and the duodenum, but not in the gastric corpus. They were also present in the proximal jejunum, rarely noted in the distal jejunum and ileum, and absent in the large intestine and the appendix vermiformis. Moreover, sst2A cells were found abundantly in the neural plexus. sst2A receptors on antral gastrin cells could mediate somatostatin inhibition on gastrin secretion, whereas those in the neural plexus could mediate somatostatin effects on motility and ion transport in the lower gastrointestinal tract. Rare sst2A cells in bronchi and bronchioles located basally and parabasally in the gastrointestinal epithelium were detected that could represent stem/progenitor cells. It is currently not clear whether and which of the identified sst2A cells are at the origin of sst2A-positive neuroendocrine gut or lung tumors.

Binding of neuropeptides to their receptors usually results in internalization of receptor-ligand complexes. This process serves a crucial role in receptor downregulation, resensitization, and transmembrane signaling. It has mainly been investigated in cells ectopically expressing recombinant receptors. In the present study, we investigated whether rat central neurons and astrocytes naturally expressing somatostatin (SRIF) receptors internalized this neuropeptide. We demonstrated that 29% of cortical and 45% of hippocampal neurons in culture expressed the SRIF receptor sst2A and that 40–50% of the neurons internalized fluorescent SRIF. Similarly, an important proportion of astrocytes expressed sst2A (up to 60% in cortical cultures) and internalized fluo-SRIF. Competition experiments using the sst2/sst5-preferring agonist SMS 201-995 (octreotide) showed that a subpopulation of neurons internalized fluo-SRIF via sst2 and/or sst5 receptors, but that others also did so via other subtypes. Fluo-SRIF labeling was barely competed for by the sst1-selective agonist CH-275, indicating that sst1 was unlikely to be mediating SRIF internalization in hippocampal and cortical neurons. Given the paucity of sst5 receptors in cerebral cortex and hippocampus and the poor yield of sst4 internalization in transfected cells, we conclude that sst2 and sst3 subtypes are the most likely to be responsible for SRIF internalization in our culture systems. Synapse 38:177–186, 2000. © 2000 Wiley-Liss, Inc.

Background In a previous study, we demonstrated the presence of receptors for somatostatin, a neuropeptide with immunoregulatory properties, in the inflammatory lesions of patients suffering from sarcoidosis and other granulomatous diseases by in vivo somatostatin receptor scintigraphy and in vitro autoradiography. However, it was not possible to identify exactly which cell types expressed the somatostatin receptors and which subtype was expressed. In this study we used a polyclonal antiserum directed against the sst2A receptor to identify more accurately the sst2A-expressing cells in sarcoidosis and other granulomatous diseases. Design Tissue biopsies from 12 patients with sarcoidosis, one patient with giant cell arteritis and one patient with Wegener's granulomatosis were studied by immunohistochemistry with the sst2A-specific antiserum. Two of the sarcoidosis patients were treated with the somatostatin analogue octreotide (100 μg t.i.d.). Results Epithelioid cells, multinucleated giant cells and a subset of CD68+ macrophages stained positive for sst2A in 9 out of 12 of the sarcoid biopsies and in both non-sarcoid granuloma biopsies. Treatment with octreotide resulted in clinical improvement in one out of two treated patients. Conclusion The identification of somatostatin receptors on granuloma macrophages, epithelioid cells and giant cells, and the successful treatment of one patient with sarcoidosis with a somatostatin analogue, may offer new possibilities for treatment of granulomatous diseases.