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) greater than NT (0.9) approximately avian XP (1.0) greater than 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 of 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 alpha-adrenoceptor blocker phentolamine (70 nM), the K(+)-channel blocker apamin (7 nM) and the Ca2(+)-channel blocker verapamil (0.7 microM). 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.
Brown
D R
DR
University of Minnesota College of Veterinary Medicine, Department of Veterinary Biology, St. Paul 55108.
Carraway
R E
RE
Parsons
A M
AM
Mitra
S P
SP
D000818:Animals; D001681:Biological Assay; D002118:Calcium / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D013552:Swine; D013618:Tachyphylaxis
D007473:Ion Channels; D009496:Neurotensin; D002118:Calcium; D009638:Norepinephrine