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Unacylated ghrelin is not a functional antagonist but a full agonist of the type 1a growth hormone secretagogue receptor (GHS-R).
Mol Cell Endocrinol. 2007 Aug 15; 274(1-2):30-4.MC

Abstract

Recent findings demonstrate that the effects of ghrelin can be abrogated by co-administered unacylated ghrelin (UAG). Since the general consensus is that UAG does not interact with the type 1a growth hormone secretagogue receptor (GHS-R), a possible mechanism of action for this antagonistic effect is via another receptor. However, functional antagonism of the GHS-R by UAG has not been explored extensively. In this study we used human GHS-R and aequorin expressing CHO-K1 cells to measure [Ca(2+)](i) following treatment with UAG. UAG at up to 10(-5)M did not antagonize ghrelin induced [Ca(2+)](i). However, UAG was found to be a full agonist of the GHS-R with an EC(50) of between 1.6 and 2 microM using this in vitro system. Correspondingly, UAG displaced radio-labeled ghrelin from the GHS-R with an IC(50) of 13 microM. In addition, GHS-R antagonists were found to block UAG induced [Ca(2+)](i) with approximately similar potency to their effect on ghrelin activation of the GHS-R, suggesting a similar mode of action. These findings demonstrate in a defined system that UAG does not antagonize activation of the GHS-R by ghrelin. But our findings also emphasize the importance of assessing the concentration of UAG used in both in vitro and in vivo experimental systems that are aimed at examining GHS-R independent effects. Where local concentrations of UAG may reach the high nanomolar to micromolar range, assignment of GHS-R independent effects should be made with caution.

Authors+Show Affiliations

Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17601657

Citation

Gauna, Carlotta, et al. "Unacylated Ghrelin Is Not a Functional Antagonist but a Full Agonist of the Type 1a Growth Hormone Secretagogue Receptor (GHS-R)." Molecular and Cellular Endocrinology, vol. 274, no. 1-2, 2007, pp. 30-4.
Gauna C, van de Zande B, van Kerkwijk A, et al. Unacylated ghrelin is not a functional antagonist but a full agonist of the type 1a growth hormone secretagogue receptor (GHS-R). Mol Cell Endocrinol. 2007;274(1-2):30-4.
Gauna, C., van de Zande, B., van Kerkwijk, A., Themmen, A. P., van der Lely, A. J., & Delhanty, P. J. (2007). Unacylated ghrelin is not a functional antagonist but a full agonist of the type 1a growth hormone secretagogue receptor (GHS-R). Molecular and Cellular Endocrinology, 274(1-2), 30-4.
Gauna C, et al. Unacylated Ghrelin Is Not a Functional Antagonist but a Full Agonist of the Type 1a Growth Hormone Secretagogue Receptor (GHS-R). Mol Cell Endocrinol. 2007 Aug 15;274(1-2):30-4. PubMed PMID: 17601657.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Unacylated ghrelin is not a functional antagonist but a full agonist of the type 1a growth hormone secretagogue receptor (GHS-R). AU - Gauna,Carlotta, AU - van de Zande,Bedette, AU - van Kerkwijk,Anke, AU - Themmen,Axel P N, AU - van der Lely,A J, AU - Delhanty,Patric J D, Y1 - 2007/05/21/ PY - 2007/01/24/received PY - 2007/05/07/revised PY - 2007/05/16/accepted PY - 2007/7/3/pubmed PY - 2007/10/24/medline PY - 2007/7/3/entrez SP - 30 EP - 4 JF - Molecular and cellular endocrinology JO - Mol Cell Endocrinol VL - 274 IS - 1-2 N2 - Recent findings demonstrate that the effects of ghrelin can be abrogated by co-administered unacylated ghrelin (UAG). Since the general consensus is that UAG does not interact with the type 1a growth hormone secretagogue receptor (GHS-R), a possible mechanism of action for this antagonistic effect is via another receptor. However, functional antagonism of the GHS-R by UAG has not been explored extensively. In this study we used human GHS-R and aequorin expressing CHO-K1 cells to measure [Ca(2+)](i) following treatment with UAG. UAG at up to 10(-5)M did not antagonize ghrelin induced [Ca(2+)](i). However, UAG was found to be a full agonist of the GHS-R with an EC(50) of between 1.6 and 2 microM using this in vitro system. Correspondingly, UAG displaced radio-labeled ghrelin from the GHS-R with an IC(50) of 13 microM. In addition, GHS-R antagonists were found to block UAG induced [Ca(2+)](i) with approximately similar potency to their effect on ghrelin activation of the GHS-R, suggesting a similar mode of action. These findings demonstrate in a defined system that UAG does not antagonize activation of the GHS-R by ghrelin. But our findings also emphasize the importance of assessing the concentration of UAG used in both in vitro and in vivo experimental systems that are aimed at examining GHS-R independent effects. Where local concentrations of UAG may reach the high nanomolar to micromolar range, assignment of GHS-R independent effects should be made with caution. SN - 0303-7207 UR - https://www.unboundmedicine.com/medline/citation/17601657/Unacylated_ghrelin_is_not_a_functional_antagonist_but_a_full_agonist_of_the_type_1a_growth_hormone_secretagogue_receptor__GHS_R__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0303-7207(07)00208-0 DB - PRIME DP - Unbound Medicine ER -