CENTRAL INHIBITORY-ACTION OF PEPTIDE YY ON GASTRIC-MOTILITY IN RATS

Specific peptide YY (PYY) binding sites have recently been identified autoradiographically in the area postrema, nucleus of the solitary tra ct, and dorsal motor nucleus regions [collectively referred to as the dorsal vagal complex (DVC)] in rats. These medullary brain stem region s are responsible for vagovagal reflex control of gastric function, in cluding gastric motility. We propose that PYY can modulate gastrointes tinal functions, such as gastric motility, by interacting with PYY bin ding sites found in DVC. Furthermore, we predict that central PYY effe cts on gastric function are mediated by the vagus nerve. In the presen t study, urethan-anesthetized rats were used. PYY (20.0 and 2.0 fmol) injected directly into DVCs of the animals produced significant inhibi tion of gastric motility that was stimulated by centrally applied thyr otropin-releasing hormone (TRH). TRH is a well-accepted central stimul ator of vagal efferent pathway to the stomach. Otherwise, an excitator y effect of PYY (2 pmol) on basal gastric motility was observed and co nsidered as being pharmacological. The inhibitory effect of PW was abo lished completely by unilateral (the injection side) cervical vagotomy , suggesting that the inhibition was vagally dependent. These results support the view that physiological concentrations of PW may inhibit p roximal gut function as part of the ''ileal brake'' mechanism by actin g directly on vagovagal control circuits in the dorsal medulla. Howeve r, extremely high doses of PYY may activate gastric function through p harmacological action at pancreatic polypeptide receptors in the DVC.