2 Peptide receptors in gut endocrine tumours WOUTER W. DE HERDER LEO J. HOFLAND AART-JAN VAN DER LELY STEVEN W. J. LAMBERTS Pancreatic islet cell tumours and carcinoids may produce one or more peptide hormones. These tumoral products are released into the circulation and subsequently transported to various target organs on which they exert their action. Generally, this excessive hormone production will be reflected by a characteristic clinical syndrome. It is possible to measure the levels of most peptides in the blood, providing suitable markers for disease stage and endocrinological activity (Reubi, 1993). In addition, the high expression of receptors for some peptides by these tumours provides other valuable tumour markers. One of these peptides is somatostatin and the research field into this peptide hormone and its structurally related analogues has rapidly expanded over the last decade (Reubi, 1993). SOMATOSTATIN, ITS RECEPTORS AND ITS EFFECTS Somatostatin, originally termed somatotrophin release inhibitory factor (SRIF), is a small cyclic peptide hormone, which is present in humans in the molecular forms SRIF-14 (consisting of 14 amino acids) and SRIF-28 (28 amino acids) (Figure 1) (Brazeau et al, 1973; Pradayrol et al, 1980). SRIF has diverse biological effects in different organ systems. In the exocrine and endocrine pancreas, locally synthesized SRIF may exert an endocrine or paracrine effect. These effects are mediated through specific SRIF receptors (ssts) on the target tissues. The presence of ssts has also been demonstrated throughout the human gastrointestinal mucosa. The gastrointestinal transit time, secretion of intestinal hormones by intestinal endocrine cells, the peptide-induced secretion of intestinal fluid and the resorption of intestinal fluid can be inhibited through the action of SRIF on these receptors (Lamberts et al, 1996). Ssts are membrane-associated receptors consisting of a single poly- peptide chain with seven transmembrane domains: extracellular domains with ligand binding sites and intracellular domains with sites linked to the BailZi2re k Clinical Gastroenterology- Vol. 10, No. 4, December 1996 ISBN O-7020-218&5 095G3528/96/040571+ 17 $12.00/00 571 Copyright @ 1996, by Baillitre Tindall All rights of reproduction in any form reserved