Structure-activity relationships of rat neuromedin U for smooth muscle contraction.
Rat neuromedin U (r-NMU) and its fragment peptide amides were synthesized by solid-phase methodology. Using a chicken crop smooth muscle contraction assay, the potency of r-NMU and its fragments relative to porcine neuromedin U-8 (p-NMU-8) was r-NMU: 10.25 +/- 2.88, r-NMU (6-23): 8.01 +/- 1.04, r-NMU (10-23): 2.76 +/- 0.46, r-NMU (13-23): 2.81 +/- 0.52, and r-NMU (16-23): 0.88 +/- 0.19, respectively. Two heptapeptides, r-NMU (17-23) and r-NMU (16-22), had a relative potency of 0.61 and 0.03 respectively, and elicited maximal contraction at a dose of 10 microM to a similar degree to p-NMU-8. The other shorter C-terminal fragments did not elicit the maximal contraction or any activity. In a rat uterus contraction assay, r-NMU (13-23), but not r-NMU (16-23), at a dose of 4 nM retained as high a stimulatory activity as r-NMU itself. r-NMU (17-22) was the smallest peptide fragment to elicit the maximal sustained contraction at 10 microM. These results indicate that the amino acid sequence Phe-Leu-Phe-Arg-Pro-Arg, corresponding to positions 17 to 22 of r-NMU, may be essential for contractile activity. N-terminal peptide segments Tyr-Gln-Gly-Pro corresponding to positions 6 to 9, and Ser-Gly-Gly corresponding to positions 13 to 15, appear to be of special importance for potent activity.
Sakura
N
N
Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Ohta
S
S
Uchida
Y
Y
Kurosawa
K
K
Okimura
K
K
Hashimoto
T
T
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009479:Neuropeptides / Q000032:analysis / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D009479:Neuropeptides; C056900:neuromedin U