MECHANISMS OF PEPTIDE YY RELEASE INDUCED BY AN INTRADUODENAL MEAL IN RATS - NEURAL REGULATION BY PROXIMAL GUT

Peptide YY (PYY) release in anaesthetized rats was studied during the 2 h following the intraduodenal administration of a semi-liquid meal o f 21 kJ. Surgical anal pharmacological manipulations were performed in order to analyse the mechanisms of PYY release. Post-prandial PYY rel ease was suppressed or strongly decreased by caecocolonectomy, truncal vagotomy, tetrodotoxin, hexamethonium, sensory denervation by perivag al capsaicin, and by the NO-synthase inhibitor L-N-arginine methyl est er, while atropine, adrenergic blockers, antagonists of type-A or type -B cholecystokinin (CCK) receptors or bombesin receptors had no effect . Comparing the digestive transit of the semi-liquid meal with the amo unt of PYY contained in the small bowel wall showed that nutrients had not reached the area rich in cells containing PYY by 30 min, the time at which there was a large PYY release in plasma. By 120 min, the mea l front had travelled 72% of the small intestine length, just beginnin g to reach the PYY-rich part of the ileum. We conclude that the main p ostprandial PYY release studied in this model comes from ileal and col onic L-cells indirectly stimulated through a neural mechanism originat ing in the proximal gut and involving sensory vagal fibres, nicotinic synapses and NO release, while CCK and bombesin do not seem to be phys iologically involved.