Ranachensinin: a novel aliphatic tachykinin from the skin secretion of the Chinese brown frog, Rana chensinensis.
Amphibian skin secretions contain a plethora of pharmacologically-active substances and represent established sources of bioactive peptides, including tachykinins. Tachykinins are one of the most widely-studied peptide families in animals and are found in neuroendocrine tissues from the lowest vertebrates to mammals. They are characterized by the presence of a highly-conserved C-terminal pentapeptide amide sequence motif (-FXGLM-amide) that also constitutes the bioactive core of the peptide. Amidation of the C-terminal methioninyl residue appears to be mandatory in the expression of biological activity. Here, we describe the isolation, characterization and molecular cloning of a novel tachykinin named ranachensinin, from the skin secretion of the Chinese brown frog, Rana chensinensis. This peptide, DDTSDRSN QFIGLM-amide, contains the classical C-terminal pentapeptide amide motif in its primary structure and an Ile (I) residue in the variable X position. A synthetic replicate of ranachensinin, synthesized by solid-phase Fmoc chemistry, was found to contract the smooth muscle of rat urinary bladder with an EC50 of 20.46 nM. However, in contrast, it was found to be of low potency in contraction of rat ileum smooth muscle with an EC50 of 2.98 µM. These data illustrate that amphibian skin secretions continue to provide novel bioactive peptides with selective effects on functional targets in mammalian tissues.
Natural Drug Discovery Research Group, School of Pharmacy, Medical Biology Centre, Queen's University, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK. l.wang@qub.ac.uk.
Yuxin
Y
Wu
Renjie
R
Li
Jie
J
Ma
Mei
M
Zhou
Lei
L
Wang
Timothy I
TI
McClure
Jiqun
J
Cai
Tianbao
T
Chen
Chris
C
Shaw
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D017124:Conserved Sequence; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000737:chemistry / Q000187:drug effects; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011898:Ranidae; D051381:Rats; D012867:Skin / Q000378:metabolism*; D015320:Tachykinins / Q000737:chemistry / Q000302:isolation & purification*
D010455:Peptides; D015320:Tachykinins