neuromedin-n and kinetensin

The action of xenin, a novel 25-residue peptide of the neurotensin (NT)/xenopsin family, was investigated in isolated rat ileal muscle strips and in dispersed longitudinal smooth muscle cells of rat small intestine in vitro. Xenin relaxes KCl-precontracted ileal strips dose dependently (1 nM-3 microM). The order of potency of the investigated peptides was as follows: xenopsin = NT = xenin > neuromedin N. Kinetensin was inactive. Tetrodotoxin, hexamethonium, tetraethylammonium, 4-aminopyridine, and NG-nitro-L-arginine did not influence the relaxant effects of xenin or NT, whereas the K+ channel blocker apamin nearly abolished their effects. Desensitization against one of the peptides or blockade of NT receptors by SR-48692 prevented the effect of xenin and NT. Structure-activity experiments revealed that the COOH-terminal part of the molecules of xenin and NT is essential for biological activity. Experiments with isolated dispersed smooth muscle cells and binding studies on intestinal smooth muscle cell membranes confirmed and extended the results obtained with muscle strips. In conclusion, xenin relaxes rat ileal smooth muscle via a muscular NT-type apamin-sensitive receptor.

Topics: Animals; Apamin; Cell Membrane; Female; Ileum; In Vitro Techniques; Male; Muscle Relaxation; Muscle, Smooth; Neurotensin; Oligopeptides; Peptide Fragments; Peptides; Rats; Receptors, Neurotensin

The effects of neurotensin and neurotensin analogues on dopamine neurones were studied in an in vitro slice preparation of rat substantia nigra, pars compacta using extracellular and intracellular recording techniques. Neurotensin had an EC50 of 13 nM in these experiments. This study showed that the C-terminal 5 amino acids of neurorotensin in neurotensin-(9-13) retained agonist activity on substantia nigra neurones. The naturally occurring neurotensin analogues neuromedin N and avian neurotensin were also active whilst kinetensin was inactive. Kinetensin differs from the C-terminal neurotensin 5-amino acids by two amino acids. The difference between the activity of neurotensin and the inactivity of kinetensin was investigated using synthetic peptides which contained single amino acid substitutions. These results show that position 12 of neurotensin is important for agonist activity in the substantia nigra.

Topics: Animals; Birds; Dopamine; Electrophysiology; In Vitro Techniques; Male; Neurons; Neurotensin; Oligopeptides; Peptide Fragments; Rats; Structure-Activity Relationship; Substantia Nigra

A novel nonapeptide with neurotensin-like immunoreactivity was isolated from pepsin-treated human plasma by dialysis, ion-exchange chromatography and high performance reversed-phase liquid chromatography. The amino acid sequence was determined by automated gas-phase sequence analysis as Ile-Ala-Arg-Arg-His-Pro-Tyr-Phe-Leu. Sequence homology with human serum albumin and with the biologically active peptides neurotensin and angiotensin is demonstrated. The name proposed for this peptide is kinetensin.

Topics: Amino Acid Sequence; Angiotensin I; Angiotensins; Animals; Cattle; Chickens; Chromatography, High Pressure Liquid; Humans; Microchemistry; Neurotensin; Oligopeptides; Pepsin A; Peptide Fragments; Peptides; Serum Albumin; Swine; Xenopus; Xenopus Proteins