Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › fagfællebedømt
Standard
Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells. / Engelstoft, Maja S; Park, Won-Mee; Sakata, Ichiro; Kristensen, Line V; Husted, Anna Sofie; Osborne-Lawrence, Sherri; Piper, Paul K; Walker, Angela K; Pedersen, Maria H; Nøhr, Mark K; Pan, Jie; Sinz, Christopher J; Carrington, Paul E; Akiyama, Taro E; Jones, Robert M; Tang, Cong; Ahmed, Kashan; Offermanns, Stefan; Egerod, Kristoffer Lihme; Zigman, Jeffrey M; Schwartz, Thue W.
I: Molecular Metabolism, Bind 2, Nr. 4, 11.2013, s. 376-92.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells
AU - Engelstoft, Maja S
AU - Park, Won-Mee
AU - Sakata, Ichiro
AU - Kristensen, Line V
AU - Husted, Anna Sofie
AU - Osborne-Lawrence, Sherri
AU - Piper, Paul K
AU - Walker, Angela K
AU - Pedersen, Maria H
AU - Nøhr, Mark K
AU - Pan, Jie
AU - Sinz, Christopher J
AU - Carrington, Paul E
AU - Akiyama, Taro E
AU - Jones, Robert M
AU - Tang, Cong
AU - Ahmed, Kashan
AU - Offermanns, Stefan
AU - Egerod, Kristoffer Lihme
AU - Zigman, Jeffrey M
AU - Schwartz, Thue W
PY - 2013/11
Y1 - 2013/11
N2 - The molecular mechanisms regulating secretion of the orexigenic-glucoregulatory hormone ghrelin remain unclear. Based on qPCR analysis of FACS-purified gastric ghrelin cells, highly expressed and enriched 7TM receptors were comprehensively identified and functionally characterized using in vitro, ex vivo and in vivo methods. Five Gαs-coupled receptors efficiently stimulated ghrelin secretion: as expected the β1-adrenergic, the GIP and the secretin receptors but surprisingly also the composite receptor for the sensory neuropeptide CGRP and the melanocortin 4 receptor. A number of Gαi/o-coupled receptors inhibited ghrelin secretion including somatostatin receptors SSTR1, SSTR2 and SSTR3 and unexpectedly the highly enriched lactate receptor, GPR81. Three other metabolite receptors known to be both Gαi/o- and Gαq/11-coupled all inhibited ghrelin secretion through a pertussis toxin-sensitive Gαi/o pathway: FFAR2 (short chain fatty acid receptor; GPR43), FFAR4 (long chain fatty acid receptor; GPR120) and CasR (calcium sensing receptor). In addition to the common Gα subunits three non-common Gαi/o subunits were highly enriched in ghrelin cells: GαoA, GαoB and Gαz. Inhibition of Gαi/o signaling via ghrelin cell-selective pertussis toxin expression markedly enhanced circulating ghrelin. These 7TM receptors and associated Gα subunits constitute a major part of the molecular machinery directly mediating neuronal and endocrine stimulation versus metabolite and somatostatin inhibition of ghrelin secretion including a series of novel receptor targets not previously identified on the ghrelin cell.
AB - The molecular mechanisms regulating secretion of the orexigenic-glucoregulatory hormone ghrelin remain unclear. Based on qPCR analysis of FACS-purified gastric ghrelin cells, highly expressed and enriched 7TM receptors were comprehensively identified and functionally characterized using in vitro, ex vivo and in vivo methods. Five Gαs-coupled receptors efficiently stimulated ghrelin secretion: as expected the β1-adrenergic, the GIP and the secretin receptors but surprisingly also the composite receptor for the sensory neuropeptide CGRP and the melanocortin 4 receptor. A number of Gαi/o-coupled receptors inhibited ghrelin secretion including somatostatin receptors SSTR1, SSTR2 and SSTR3 and unexpectedly the highly enriched lactate receptor, GPR81. Three other metabolite receptors known to be both Gαi/o- and Gαq/11-coupled all inhibited ghrelin secretion through a pertussis toxin-sensitive Gαi/o pathway: FFAR2 (short chain fatty acid receptor; GPR43), FFAR4 (long chain fatty acid receptor; GPR120) and CasR (calcium sensing receptor). In addition to the common Gα subunits three non-common Gαi/o subunits were highly enriched in ghrelin cells: GαoA, GαoB and Gαz. Inhibition of Gαi/o signaling via ghrelin cell-selective pertussis toxin expression markedly enhanced circulating ghrelin. These 7TM receptors and associated Gα subunits constitute a major part of the molecular machinery directly mediating neuronal and endocrine stimulation versus metabolite and somatostatin inhibition of ghrelin secretion including a series of novel receptor targets not previously identified on the ghrelin cell.
U2 - 10.1016/j.molmet.2013.08.006
DO - 10.1016/j.molmet.2013.08.006
M3 - Journal article
C2 - 24327954
VL - 2
SP - 376
EP - 392
JO - Molecular Metabolism
JF - Molecular Metabolism
SN - 2212-8778
IS - 4
ER -
ID: 117973224