Neurotensin-related peptides inhibit spontaneous longitudinal contractions of porcine distal jejunum

The tridecapeptide neurotensin (NT) and its C-terminal homologs, including xenopsin (XP) and neuromedin N (NM-N), reduced the amplitude of spontaneous contractions in longitudinal smooth muscle strips from the porcine distal jejunum in vitro. The rank order of potency (IC₅₀ in nM) was XP (0.1) > NT (0.9) ≈ avian XP (1.0) > NM-N (1.6), which could not be explained on the basis of differential peptide degradation. Tachyphylaxis and cross-tachyphylaxis were observed after repeated NT and XP addition to muscle strips. The action NT was mimicked by norepinephrine (NE), but not by opioid peptides, somatostatin, or vasoactive intestinal peptide. NE was nearly 100-fold less potent than NT and did not produce a state of tachyphylaxis to NT. The effects of NT and NE were unaltered by the neuronal conduction blocker tetrodotoxin (70 nM). However, the actions of NE, unlike those of NT, were reduced by the α-adrenoceptor blocker phentolamine (70 nM), the K⁺-channel blocker apamin (7 nM) and the Ca²⁺-channel blocker verapamil (0.7 μM). These results suggest that NT and related peptides, through a nonadrenergic mechanism, interact with smooth muscle receptors to modulate jejunoileal motor function in the pig.