title: A transplantable phosphorylation probe for direct assessment of G protein-coupled receptor activation.
abstract: The newly developed multireceptor somatostatin analogs pasireotide (SOM230), octreotide and somatoprim (DG3173) have primarily been characterized according to their binding profiles. However, their ability to activate individual somatostatin receptor subtypes (sst) has not been directly assessed so far. Here, we transplanted the carboxyl-terminal phosphorylation motif of the sst(2) receptor to other somatostatin receptors and assessed receptor activation using a set of three phosphosite-specific antibodies. Our comparative analysis revealed unexpected efficacy profiles for pasireotide, octreotide and somatoprim. Pasireotide was able to activate sst(3) and sst(5) receptors but was only a partial agonist at the sst(2) receptor. Octreotide exhibited potent agonistic properties at the sst(2) receptor but produced very little sst(5) receptor activation. Like octreotide, somatoprim was a full agonist at the sst(2) receptor. Unlike octreotide, somatoprim was also a potent agonist at the sst(5) receptor. Together, we propose the application of a phosphorylation probe for direct assessment of G protein-coupled receptor activation and demonstrate its utility in the pharmacological characterization of novel somatostatin analogs.
authors: Department of Pharmacology and Toxicology, Jena University Hospital-Friedrich Schiller University Jena, Jena, Germany.
authors: Andrea
authors: A
authors: Kliewer
authors: Anika
authors: A
authors: Mann
authors: Aline
authors: A
authors: Petrich
authors: Florian
authors: F
authors: Pöll
authors: Stefan
authors: S
authors: Schulz
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D006801:Humans; D007150:Immunohistochemistry; D015282:Octreotide / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D009842:Oligopeptides; C420459:PTR 3173; D043562:Receptors, G-Protein-Coupled; D017481:Receptors, Somatostatin; D013004:Somatostatin; C517782:pasireotide; D015282:Octreotide