Peptide-YY-(l-36) [PYY-(l-36)] is an endocrine peptide that is found primarily in the mucosal layer of the colon. We reported previously that a direct intracolonic (IC) infusion of amino acids in dogs resulted in a robust release of PYY compared to other nutrients (fat, glucose, and protein). The objective of this study was to investigate the possible mechanisms underlying the release of PYY in response to IC infusion of amino acids. Intracolonic infusion of a mixture of tryptophan and phenylalanine (Trp+Phe; 100 mM; 200 ml/h) resulted in a significant release of PYY [integrated PYY release, 74.5 ± 14.0 ng (0120 min)/ml], which was not affected by iv atropine, hexamethonium, or propranolol treatment. Intravenous infusion of Trp+Phe failed to release PYY [integrated PYY release, —0.6 ± 0.9 ng (0-120 min)/ml]. Intracolonic infusion of aromatic amino acids (Trp+Phe) was more potent in releasing PYY than aliphatic (leucine and glycine) and charged (arginine) amino acids. PYY release in response to IC infusion of the deamino and decarboxylated forms of Phe was significantly (P < 0.05) decreased [integrated PYY release, 17.5 ± 2.6 and 12.1 ± 2.8 ng (0-120 min)/ml, respectively] compared to that in response to intact Phe [integrated PYY release, 39.4 ± 4.3 ng (0-120 min)/ml]. These results suggest that 1) PYY release in response to IC administered amino acids is independent of ganglionic, cholinergic, and d-adrenergic transmission; 2) PYY release in response to IC amino acids is due to a direct contact of amino acids with the luminal pole of PYY cells in the colon and is not the result of a stimulatory action of amino acids via the general circulation; and 3) the amino and carboxylic groups of an amino acid as well as the ring structures of aromatic amino acids are structural requirements for PYY release.
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