Species-specific action of (Pro3)GIP - an efficacious agonist on human GIP receptor, but partial agonist and competitive antagonist on rat and mouse GIP receptors

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

Species-specific action of (Pro3)GIP - an efficacious agonist on human GIP receptor, but partial agonist and competitive antagonist on rat and mouse GIP receptors. / Sparre-Ulrich, A H; Hansen, Lærke Smidt; Svendsen, B; Christensen, M; Knop, F K; Hartmann, B; Holst, J J; Rosenkilde, M M.

I: British Journal of Pharmacology, Bind 173, Nr. 1, 01.2016, s. 27-38.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Sparre-Ulrich, AH, Hansen, LS, Svendsen, B, Christensen, M, Knop, FK, Hartmann, B, Holst, JJ & Rosenkilde, MM 2016, 'Species-specific action of (Pro3)GIP - an efficacious agonist on human GIP receptor, but partial agonist and competitive antagonist on rat and mouse GIP receptors', British Journal of Pharmacology, bind 173, nr. 1, s. 27-38. https://doi.org/10.1111/bph.13323

APA

Sparre-Ulrich, A. H., Hansen, L. S., Svendsen, B., Christensen, M., Knop, F. K., Hartmann, B., ... Rosenkilde, M. M. (2016). Species-specific action of (Pro3)GIP - an efficacious agonist on human GIP receptor, but partial agonist and competitive antagonist on rat and mouse GIP receptors. British Journal of Pharmacology, 173(1), 27-38. https://doi.org/10.1111/bph.13323

Vancouver

Sparre-Ulrich AH, Hansen LS, Svendsen B, Christensen M, Knop FK, Hartmann B o.a. Species-specific action of (Pro3)GIP - an efficacious agonist on human GIP receptor, but partial agonist and competitive antagonist on rat and mouse GIP receptors. British Journal of Pharmacology. 2016 jan;173(1):27-38. https://doi.org/10.1111/bph.13323

Author

Sparre-Ulrich, A H ; Hansen, Lærke Smidt ; Svendsen, B ; Christensen, M ; Knop, F K ; Hartmann, B ; Holst, J J ; Rosenkilde, M M. / Species-specific action of (Pro3)GIP - an efficacious agonist on human GIP receptor, but partial agonist and competitive antagonist on rat and mouse GIP receptors. I: British Journal of Pharmacology. 2016 ; Bind 173, Nr. 1. s. 27-38.

Bibtex

@article{077ded48e67a49d68113b0255a8a6605,
title = "Species-specific action of (Pro3)GIP - an efficacious agonist on human GIP receptor, but partial agonist and competitive antagonist on rat and mouse GIP receptors",
abstract = "BACKGROUND AND PURPOSE: Specific high potent receptor antagonists are valuable tools when evaluating animal and human physiology. Within the glucose-dependent insulinotropic polypeptide (GIP) system, considerable attention has been given to the presumed GIP receptor antagonist (Pro3)GIP and its effect in murine studies. We conducted a pharmacological analysis of this ligand including interspecies differences between the rodent and human GIP system.EXPERIMENTAL APPROACH: Transiently transfected COS-7 cells were assessed for cAMP accumulation upon ligand stimulation and assayed in competition binding using (125) I-human GIP. Using isolated perfused rodent pancreata both from wild type and GIPR-deficient animals, insulin-, glucagon-, and somatostatin-releasing properties in response to species-specific GIP and (Pro3)GIP analogues were evaluated.KEY RESULTS: Human (Pro3)GIP is an efficacious agonist on the human GIPR with similar efficacy (Emax ) in cAMP production as human GIP, while both rat and mouse(Pro3)GIP were partial agonists on their corresponding receptors. Rodent GIPs are more potent and efficacious at their receptors than human GIP. In perfused pancreata at 7 mM glucose, both rodent (Pro3)GIP analogues induced modest insulin, glucagon and somatostatin secretion corresponding to the partial agonism observed in cAMP production. Conclusions and Implications When evaluating compound properties it is important to consider interspecies differences both at the receptor and ligand level. Thus, in rodent models human GIP is a comparatively weak partial agonist. Human (Pro3)GIP is not an effective antagonist, so there is still a need for an effective antagonist for the elucidation of GIP's physiology.",
author = "Sparre-Ulrich, {A H} and Hansen, {L{\ae}rke Smidt} and B Svendsen and M Christensen and Knop, {F K} and B Hartmann and Holst, {J J} and Rosenkilde, {M M}",
note = "This article is protected by copyright. All rights reserved.",
year = "2016",
month = "1",
doi = "10.1111/bph.13323",
language = "English",
volume = "173",
pages = "27--38",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley",
number = "1",

}

RIS

TY - JOUR

T1 - Species-specific action of (Pro3)GIP - an efficacious agonist on human GIP receptor, but partial agonist and competitive antagonist on rat and mouse GIP receptors

AU - Sparre-Ulrich, A H

AU - Hansen, Lærke Smidt

AU - Svendsen, B

AU - Christensen, M

AU - Knop, F K

AU - Hartmann, B

AU - Holst, J J

AU - Rosenkilde, M M

N1 - This article is protected by copyright. All rights reserved.

PY - 2016/1

Y1 - 2016/1

N2 - BACKGROUND AND PURPOSE: Specific high potent receptor antagonists are valuable tools when evaluating animal and human physiology. Within the glucose-dependent insulinotropic polypeptide (GIP) system, considerable attention has been given to the presumed GIP receptor antagonist (Pro3)GIP and its effect in murine studies. We conducted a pharmacological analysis of this ligand including interspecies differences between the rodent and human GIP system.EXPERIMENTAL APPROACH: Transiently transfected COS-7 cells were assessed for cAMP accumulation upon ligand stimulation and assayed in competition binding using (125) I-human GIP. Using isolated perfused rodent pancreata both from wild type and GIPR-deficient animals, insulin-, glucagon-, and somatostatin-releasing properties in response to species-specific GIP and (Pro3)GIP analogues were evaluated.KEY RESULTS: Human (Pro3)GIP is an efficacious agonist on the human GIPR with similar efficacy (Emax ) in cAMP production as human GIP, while both rat and mouse(Pro3)GIP were partial agonists on their corresponding receptors. Rodent GIPs are more potent and efficacious at their receptors than human GIP. In perfused pancreata at 7 mM glucose, both rodent (Pro3)GIP analogues induced modest insulin, glucagon and somatostatin secretion corresponding to the partial agonism observed in cAMP production. Conclusions and Implications When evaluating compound properties it is important to consider interspecies differences both at the receptor and ligand level. Thus, in rodent models human GIP is a comparatively weak partial agonist. Human (Pro3)GIP is not an effective antagonist, so there is still a need for an effective antagonist for the elucidation of GIP's physiology.

AB - BACKGROUND AND PURPOSE: Specific high potent receptor antagonists are valuable tools when evaluating animal and human physiology. Within the glucose-dependent insulinotropic polypeptide (GIP) system, considerable attention has been given to the presumed GIP receptor antagonist (Pro3)GIP and its effect in murine studies. We conducted a pharmacological analysis of this ligand including interspecies differences between the rodent and human GIP system.EXPERIMENTAL APPROACH: Transiently transfected COS-7 cells were assessed for cAMP accumulation upon ligand stimulation and assayed in competition binding using (125) I-human GIP. Using isolated perfused rodent pancreata both from wild type and GIPR-deficient animals, insulin-, glucagon-, and somatostatin-releasing properties in response to species-specific GIP and (Pro3)GIP analogues were evaluated.KEY RESULTS: Human (Pro3)GIP is an efficacious agonist on the human GIPR with similar efficacy (Emax ) in cAMP production as human GIP, while both rat and mouse(Pro3)GIP were partial agonists on their corresponding receptors. Rodent GIPs are more potent and efficacious at their receptors than human GIP. In perfused pancreata at 7 mM glucose, both rodent (Pro3)GIP analogues induced modest insulin, glucagon and somatostatin secretion corresponding to the partial agonism observed in cAMP production. Conclusions and Implications When evaluating compound properties it is important to consider interspecies differences both at the receptor and ligand level. Thus, in rodent models human GIP is a comparatively weak partial agonist. Human (Pro3)GIP is not an effective antagonist, so there is still a need for an effective antagonist for the elucidation of GIP's physiology.

U2 - 10.1111/bph.13323

DO - 10.1111/bph.13323

M3 - Journal article

C2 - 26359804

VL - 173

SP - 27

EP - 38

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 1

ER -

ID: 150708073