title: Antisecretory Effects of Chimeric Somatostatin/Dopamine Receptor Ligands on Gastroenteropancreatic Neuroendocrine Tumors.
abstract: The recent finding that gastroenteropancreatic neuroendocrine tumors expressed the dopaminergic D2 receptor in addition to somatostatin (sst) receptors suggested that multiple targeting approaches might decrease hormone hypersecretion more effectively than sst agonists alone.
  
  
  
  To test this hypothesis, (i) we measured the expression of sst receptor type 2 (sst2 receptor) and D2 receptor in 11 gastroenteropancreatic neuroendocrine tumors and (ii) we compared the ability of lanreotide, cabergoline, their combination, and sst/D2 chimeric ligands to decrease chromogranin A (CgA), gastrin, or serotonin release in primary cultures derived from these tumors.
  
  
  
  Moderate to high positivity was observed for sst2 receptor and D2 receptor, the latter being more expressed in pancreatic tumors. Lanreotide decreased CgA secretion in all cultures, but only 3 tumors responded to cabergoline. No additivity was observed in lanreotide. BIM 23A781 decreased CgA release to the same extent as lanreotide, whereas the other chimeric ligands were less efficient. However, BIM 23A781 was 50 times less potent than lanreotide. Similar patterns were found for gastrin or serotonin.
  
  
  
  No improvement was brought by the sst/D2 combination or chimeric ligands. Factors that underlie these tissue-specific differences remain to be elucidated.
authors.affiliation: From the *Faculté de Médecine Xavier Bichat, INSERM U1149, Centre de Recherche sur l'Inflammation (CRI), DHU Unity, Université Paris Diderot; †Université Paris Diderot; ‡Département de Pathologie Beaujon-Bichat, Hôpital Bichat, DHU UNITY, AP-HP, Paris; and §Département de Chirurgie Pancréatico-Biliaire and ∥Département de Gastroentérologie-Pancréatologie, Hôpital Beaujon, DHU UNITY, AP-HP, Clichy, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Couvelard
authors.forename: Didier
authors.initials: D
authors.lastname: Pélaprat
authors.forename: Safi
authors.initials: S
authors.lastname: Dokmak
authors.forename: Alain
authors.initials: A
authors.lastname: Sauvanet
authors.forename: Thierry
authors.initials: T
authors.lastname: Voisin
authors.forename: Alain
authors.initials: A
authors.lastname: Couvineau
authors.forename: Philippe
authors.initials: P
authors.lastname: Ruszniewski
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000077465:Cabergoline; D053379:Chromogranin A / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D004873:Ergolines / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007414:Intestinal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008024:Ligands; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000819:agonists / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D053379:Chromogranin A; D004873:Ergolines; D008024:Ligands; D010456:Peptides, Cyclic; D017448:Receptors, Dopamine D2; D017481:Receptors, Somatostatin; C060347:lanreotide; D012701:Serotonin; D013004:Somatostatin; C531242:TBR-760; D000077465:Cabergoline; D004298:Dopamine