| First Author | Engelstoft MS | Year | 2013 |
| Journal | Mol Metab | Volume | 2 |
| Issue | 4 | Pages | 376-92 |
| PubMed ID | 24327954 | Mgi Jnum | J:303659 |
| Mgi Id | MGI:6693546 | Doi | 10.1016/j.molmet.2013.08.006 |
| Citation | Engelstoft MS, et al. (2013) Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells. Mol Metab 2(4):376-92 |
| abstractText | 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 Galphas-coupled receptors efficiently stimulated ghrelin secretion: as expected the beta1-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 Galphai/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 Galphai/o- and Galphaq/11-coupled all inhibited ghrelin secretion through a pertussis toxin-sensitive Galphai/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 Galpha subunits three non-common Galphai/o subunits were highly enriched in ghrelin cells: GalphaoA, GalphaoB and Galphaz. Inhibition of Galphai/o signaling via ghrelin cell-selective pertussis toxin expression markedly enhanced circulating ghrelin. These 7TM receptors and associated Galpha 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. |
