Comprehensive Profiling of GPCR Expression in Ghrelin-Producing Cells

Area of Science:

• Endocrinology
• Molecular Cell Biology

Background:

• G protein-coupled receptors (GPCRs) are crucial in regulating cellular functions, including hormone secretion.
• Ghrelin, a peptide hormone, plays a significant role in appetite regulation and energy homeostasis.
• Understanding GPCR signaling in ghrelin-producing cells is key to deciphering ghrelin secretion control.

Purpose of the Study:

• To comprehensively map the GPCR expression profile in ghrelin-producing cells.
• To investigate the functional role of identified GPCRs in modulating ghrelin secretion.
• To identify novel signaling pathways that regulate ghrelin release.

Main Methods:

• RNA sequencing of the ghrelin-producing cell line MGN3-1 to determine GPCR expression.
• Ligand stimulation assays to analyze intracellular signaling pathways (Gs, Gq, Gi).
• Fluorescence-activated cell sorting (FACS) for validating GPCR expression in primary cells.

Main Results:

• High expression of GPCRs including adrenergic-β1 receptor, GPR81, oxytocin receptor, GPR120, and somatostatin receptor 2 was confirmed.
• Prostaglandin E2 (acting on EP4 receptor) significantly stimulated the Gs pathway and ghrelin secretion.
• Tryptophan (acting on GPR142) was identified as a novel stimulator of ghrelin secretion.
• Cholinergic receptor activation by muscarine modulated intracellular signaling but suppressed forskolin-induced ghrelin secretion.

Conclusions:

• A comprehensive GPCR expression profile in ghrelin-producing cells was established.
• Prostaglandin E2 and tryptophan represent novel regulators of ghrelin secretion.
• These findings enhance the understanding of ghrelin physiology and offer potential targets for ghrelin-modulating therapies.