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Pharmacological Characterization of Veldoreotide as a Somatostatin Receptor 4 Agonist

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) c...

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Autores principales: Dasgupta, Pooja, Gűnther, Thomas, Schulz, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541358/
https://www.ncbi.nlm.nih.gov/pubmed/34685446
http://dx.doi.org/10.3390/life11101075
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author Dasgupta, Pooja
Gűnther, Thomas
Schulz, Stefan
author_facet Dasgupta, Pooja
Gűnther, Thomas
Schulz, Stefan
author_sort Dasgupta, Pooja
collection PubMed
description 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 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 (E(max), 99.5% vs. 27.4% and 52.0%, respectively). Veldoreotide also activated SSTR2 and SSTR5 (E(max), 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.
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spelling pubmed-85413582021-10-24 Pharmacological Characterization of Veldoreotide as a Somatostatin Receptor 4 Agonist Dasgupta, Pooja Gűnther, Thomas Schulz, Stefan Life (Basel) 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 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 (E(max), 99.5% vs. 27.4% and 52.0%, respectively). Veldoreotide also activated SSTR2 and SSTR5 (E(max), 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. MDPI 2021-10-12 /pmc/articles/PMC8541358/ /pubmed/34685446 http://dx.doi.org/10.3390/life11101075 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dasgupta, Pooja
Gűnther, Thomas
Schulz, Stefan
Pharmacological Characterization of Veldoreotide as a Somatostatin Receptor 4 Agonist
title Pharmacological Characterization of Veldoreotide as a Somatostatin Receptor 4 Agonist
title_full Pharmacological Characterization of Veldoreotide as a Somatostatin Receptor 4 Agonist
title_fullStr Pharmacological Characterization of Veldoreotide as a Somatostatin Receptor 4 Agonist
title_full_unstemmed Pharmacological Characterization of Veldoreotide as a Somatostatin Receptor 4 Agonist
title_short Pharmacological Characterization of Veldoreotide as a Somatostatin Receptor 4 Agonist
title_sort pharmacological characterization of veldoreotide as a somatostatin receptor 4 agonist
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541358/
https://www.ncbi.nlm.nih.gov/pubmed/34685446
http://dx.doi.org/10.3390/life11101075
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