Structural characterisation and pharmacology of KHEYLRFamide (AF2) and KSAYMRFamide (PF3/AF8) from Haemonchus contortus

Nicola Marks, N.C. Sangster, Aaron Maule, D W Halton, D.P. Thompson, T.G. Geary, Christopher Shaw

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

The FMRFamide-related peptides (FaRPs), KHEYLRFamide (AF2) and KSAYMRFamide (PF3) were structurally characterised from the parasitic nematode of sheep, Haemonchus contortus (MH isolate). Both peptides were sequenced in a single gas-phase sequencing run and their structure confirmed by mass spectrometry which identified peptides of 920 Da (C-terminally amidated AF2) and 902/918 Da (C-terminally amidated non-oxidised/oxidised PF3, respectively). AF2 had inhibitory effects on H. contortus muscle and inhibited acetylcholine (ACh, 10 mu M)-induced contractions, with a threshold for activity of I mu M. PF3 induced concentration-dependent contractions of H. contortus (activity threshold, 10 nM) and enhanced ACh contractions. Compared with the MH isolate, an isolate of H. contortus which has reduced sensitivity to cholinergic drugs (Lawes isolate) was less sensitive to the effects of PF3. The concentration-response curves for the cholinergic compounds ACh and levamisole (LEV), and PF3, but not a control, KPNFIRFamide (PF4), showed a statistically similar shift. This study implicates PF3 in the modulation of cholinergic function in H. contortus. (C) 1999 Elsevier Science B.V. All rights reserved.
Original languageEnglish
Pages (from-to)185-194
Number of pages10
JournalMolecular and Biochemical Parasitology
Volume100
Issue number2
Publication statusPublished - 25 May 1999

ASJC Scopus subject areas

  • Molecular Biology
  • Parasitology

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