Isolation, structural characterization, and bioactivity of a novel neuromedin U analog from the defensive skin secretion of the Australasian tree frog, Litoria caerulea.
We report the isolation of a novel bioactive peptide, neuromedin U-23 (NmU-23), from the defensive skin secretion of the Australasian tree frog, Litoria caerulea. The primary structure of the peptide was established by a combination of microsequencing, mass spectroscopy and site-directed antiserum immunoreactivity as SDEEVQVPGGVISNGYFLFRPRN-amide (M(r) 2580.6). A synthetic replicate of frog NmU-23 displaced monoradioiodinated rat NmU-23 from uterine membranes in a dose-dependent fashion indistinguishable from nonisotopically labeled rat NmU-23. In a rat uterine smooth muscle strip preparation, synthetic frog NmU-23 produced dose-dependent contractions identical to porcine NmU-25. However, in a preparation of human urinary bladder muscle strip, the synthetic frog peptide was more potent than porcine NmU-25 in eliciting contraction and produced desensitization of the preparation to the latter peptide. This report demonstrates that the defensive skin secretion of a frog contains a novel peptide exhibiting a high degree of primary structural similarity to the endogenous vertebrate peptide, NmU, and that this frog skin analog displays biological activity in mammalian tissues.
Salmon
A L
AL
Natural Drug Discovery Laboratory, Clinical Medicine, The Queen's University of Belfast, Belfast, BT12 6BJ, Northern Ireland.
Johnsen
A H
AH
Bienert
M
M
McMurray
G
G
Nandha
K A
KA
Bloom
S R
SR
Shaw
C
C
D000595:Amino Acid Sequence; D000818:Animals; D002025:Bufonidae; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000378:metabolism*
D009479:Neuropeptides; C056900:neuromedin U