Peptide YY and the Y2 agonist PYY-(13-36) inhibit neurons of the dorsal motor nucleus of the vagus.

Peptide YY (PYY) is released by endocrine cells in the ileum in response to the presence of fatty acids in the intestinal lumen. Circulating PYY suppresses vagally mediated digestive functions as a consequence of direct action on neurons in the dorsal medulla. Recent evidence from our laboratory suggests that this PYY-mediated inhibition of digestion occurs because of peptide action at the Y2-type receptor in the dorsal medullary region encompassing vago-vagal reflex circuitry. The present study describes the effects of PYY and the specific Y2 agonist peptide PYY-(13-36) on neurons of the dorsal motor nucleus of the vagus (DMN) in both the 1) intact in vivo and 2) in vitro brain stem slice preparation. Our results show that 50% of DMN neurons recorded under in vivo or in vitro conditions, including synaptic blockade, are inhibited by the application of PYY or PYY-(13-36). Approximately 45% are not affected, and only approximately 5% are activated. These results suggest that one of the principal means by which PYY suppresses digestive functions is by the direct inhibition of cholinergic vagal efferent neurons of the DMN via action at a Y2 receptor.