Aims: 

Food intake is inhibited by the intestinal hormones CCK and PYY which act via vagal afferent neurons. We examined how CCK regulates the expression of Y2R, at which PYY3-36 acts, in these neurons.

Methods: 

Receptor expression was studied by immunohistochemistry and qPCR of nodose ganglia from rats fasted up to 48h, or treated with CCK8, or the CCK1 receptor antagonist lorglumide. Expression of a Y2R promoter-luciferase (Y2-luc) reporter was examined in cultured vagal afferent neurons.

Results: 

There was a significant five-fold decrease (p < 0.05) of Y2R mRNA in nodose ganglia of fasted rats compared with controls. CCK8 (10 nmol, i.p.) significantly increased Y2R mRNA in fasted rats, as did re-feeding. The latter response was inhibited by lorglumide. Y2R immunoreactivity was localised to glial cells and neurons most of which (89 ± 4%) expressed CCK1 receptors. Retrograde tracing indicated that in fasted rats there was a significant decrease in the number of Y2R-immunoreactive neurons projecting to the stomach but no change in those projecting to the proximal colon. Following transfection of Y2-luc into cultured nodose neurons, there was a 12.3 ± 0.1-fold increase in luciferase activity in response to 10 nM CCK that was abolished by the protein kinase C inhibitor Ro-32-0432 (1.5 ± 0.4, p < 0.01) and replicated by phorbol ester (16.2 ± 0.4 fold increase).

Conclusions: 

Y2R is expressed by neurons and glial cells in nodose ganglia; expression in neurons projecting to the stomach is decreased by fasting and restored by CCK. CCK stimulates Y2R expression via a PKC dependent mechanism.