Nicotine directly stimulates ghrelin secretion via α4β2 nicotinic acetylcholine receptors in gastric cells

The orexigenic peptide ghrelin is known for stimulating appetite and growth hormone release, and has been implicated in tobacco addiction. However, the direct cellular mechanisms by which tobacco-related chemicals, particularly nicotine, influence ghrelin secretion have been unclear. Current understanding lacks detail on specific receptor involvement, creating a gap in linking nicotine's psychoactive effects to ghrelin's metabolic and addictive roles. This study investigates the cellular-level interaction between nicotine and ghrelin-producing cells.

Researchers screened tobacco-related chemicals, focusing on nicotine's effects on ghrelin regulation in MGN3-1 ghrelin-producing cells. They utilized a newly developed ghrelin-HiBiT assay system to evaluate ghrelin secretion. Cells were treated with nicotine alone, or in combination with isoproterenol and oxytocin. Receptor expression was assessed, and the α4β2 selective agonist epibatidine was used to probe intracellular Ca2+ elevation, indicating receptor activation.

Nicotine alone modestly stimulated ghrelin secretion from MGN3-1 cells. Crucially, nicotine also enhanced the stimulatory effects of both isoproterenol and oxytocin on ghrelin secretion, suggesting a synergistic or sensitizing mechanism. Further investigation revealed that MGN3-1 cells expressed high levels of the α4β2 nicotinic acetylcholine receptor (nAChR). > The α4β2 selective agonist, epibatidine, evoked substantial intracellular Ca2+ elevation, confirming the functional presence and activation of these receptors in ghrelin-producing cells. These findings strongly indicate a direct role for nAChR, specifically the α4β2 subtype, in modulating ghrelin secretion.