title: Lack of evidence for cross-competition between vasoactive intestinal peptide and somatostatin at their respective receptors.
abstract: A possible cross-competition between vasoactive intestinal peptide (VIP) and somatostatin (somatotropin release inhibiting factor; SRIF) and their respective receptors, was investigated at native or recombinant SRIF and VIP/pituitary adenylate cyclase-activating polypeptide (PACAP) receptors. The activity of VIP was examined in radioligand binding assays at mouse sst(1-5), rat sst(1-2) and human sst(1-5) receptors; or at human tumours preferentially expressing each of the five SRIF receptors. Moreover, SRIF was investigated at human tumoral tissues known to exclusively express specific VIP/PACAP receptor(s). VIP had no significant effect on any of the radioligand binding sites of the SRIF receptor family of rat, mouse or human origin tested. Conversely, SRIF did not interfere with the human VIP/PACAP binding sites tested. Taken together, the results cast reservation on the claimed cross-competition between VIP and SRIF at, specifically human sst(3) receptors, or any of the cloned SRIF or VIP/PACAP receptors recognised to date.
authors.affiliation: Nervous System Research, WSJ.386.745, Novartis Pharma AG, CH-4002 Basel, Switzerland.
authors.forename: J P
authors.initials: JP
authors.lastname: Hannon
authors.forename: D
authors.initials: D
authors.lastname: Langenegger
authors.forename: B
authors.initials: B
authors.lastname: Waser
authors.forename: D
authors.initials: D
authors.lastname: Hoyer
authors.forename: J C
authors.initials: JC
authors.lastname: Reubi
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D010456:Peptides, Cyclic / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism* / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C495401:ADCYAP1 protein, human; C495402:Adcyap1 protein, mouse; C495403:Adcyap1 protein, rat; D007457:Iodine Radioisotopes; D009479:Neuropeptides; D010456:Peptides, Cyclic; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D017481:Receptors, Somatostatin; D018005:Receptors, Vasoactive Intestinal Peptide; D011994:Recombinant Proteins; C089777:Ro 25-1553; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin