Pharmacological Characterization of Veldoreotide as a Somatostatin Receptor 4 Agonist

Pharmacological Characterization of Veldoreotide as a Somatostatin Receptor 4 Agonist

Blog Article

Veldoreotide, a somatostatin analogue, binds to the somatostatin receptors (SSTR) 2, 4, and 5.The current aim was to assess its pharmacological activity as an SSTR4 agonist.G-protein signaling was assessed using a fluorescence-based membrane potential assay in human embryonic kidney 293 (HEK293) cells stably co-expressing G-protein-coupled inwardly rectifying potassium 2 channels and the individual SSTR2, SSTR4, and SSTR5, and in human BON-1 cells stably expressing these SSTRs.Veldoreotide effects on chromogranin A (CgA) secretion and cell proliferation m02n3ll/a were examined in BON-1 cells.

In HEK293 transfected cells, veldoreotide showed a high efficacy for activating the SSTR4; octreotide and pasireotide had little activity (Emax, 99.5% vs.27.4% and 52.

0%, respectively).Veldoreotide also activated arla eagle rock SSTR2 and SSTR5 (Emax, 98.4% and 96.9%, respectively).

In BON-1 cells, veldoreotide activated SSTR2, SSTR4, and SSTR5 with high potency and efficacy.CgA secretion was decreased to a greater degree in the BON-1 cells expressing SSTR4 versus the cells expressing SSTR2 and SSTR5 (65.3% vs.80.

3% and 77.6%, respectively).In the BON-1 cells expressing SSTR4, veldoreotide inhibited cell proliferation more than somatostatin SS-14 (71.2% vs.

79.7%) and to a similar extent as the SSTR4 agonist J-2156 in the presence of SSTR2 and SSTR5 antagonists.Veldoreotide is a full agonist of SSTR2, SSTR4, and SSTR5.