Peripheral opioid receptors mediate gastrointestinal secretory and motor effects of dermorphin N-terminal tetrapeptide (NTT) in the dog.

Dermorphin N-terminal-tetrapeptide-amide (NTT) increased both basal and pentagastrin- or histamine-induced secretion in conscious dogs chronically implanted with both gastric fistulae and Heidenhain pouches. These excitatory effects were significantly prevented by the opioid receptor antagonists naloxone and N-methyl-levallorphan-methanesulphonate. In conscious dogs fitted with electrodes and strain-gauges in different parts of gastrointestinal tract, a premature phase III of the migrating myoelectric complex (MMC) in the duodeno-jejunum was triggered by NTT, while the activity of the antrum was not significantly modified. Further, the peptide enhanced the contractile activity of both proximal and distal portions of the colon, including a long-lasting period of increased muscle tone on the distal colon. Either naloxone or N-methyl-levallorphan-methanesulphonate completely prevented motor effects of NTT on gastrointestinal tract. It is concluded that NTT displays significant opiate-like activity on gastric acid secretion and intestinal motility of the dog by activating peripheral mu opioid receptors.