Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.554234
Title: Molecular characterisation of selected neuropeptides from ovine intestinal tissue and from the ovine parasite Moniezie expansa
Author: Madavo, Crispin
Awarding Body: University of Ulster
Current Institution: Ulster University
Date of Award: 2008
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Abstract:
Neuropeptides native to parasitic flatworms, such as Neuropeptide F (NPF) and GNFFRFamide in Moniezia expansa, the sheep tapeworm, are believed to play vital survival roles in the parasites and therefore offer potential as anthelmintic drug targets based on knowledge of their primary structures. The gene sequence of GNFFRFamide is unknown, and doubts exist about whether only one primary structure of NPF exists. Both aspects have been investigated in this study. Vasoactive intestinal peptide (VIP) whose primary structure is highly conserved in mammals and to a lesser extent in non-mammalian vertebrates, has so far only been isolated and characterised in mammals and other vertebrates, in which it has been found to have a number of vital functions. Elucidation of the primary structure of VIP in a parasitic cestode is of interest both evolutionarily and because of the potential for its exploitation as an anthelmintic drug target. A previous study revealed the existence of molecules immunoreactive to mammalian VIP (VIP-IR) and peptide histidine isoleucine (PHI-IR) in M expansa whose chromatographic properties suggested that they may be identical to the mammalian orthologs - a surprising observation in view of the large phylogenetic difference between the species involved. Transfer of the PHI/VIP gene from the ovine host to the tapeworm parasite, previously suggested as a possible explanation for the observation, was investigated in the present study. Genomic methods failed to detect VIP cDNA in M expansa although NPF cDNA and sequences which may code for GNFFRFamide and for a number of other peptides which may be involved in important functions were amplified. Three different peptide extraction methods combined with mass spectrometry failed to detect VIP in homogenized M expansa tissue, possibly due to its low abundance. Other peptides, including putative neuropeptides, were detected in the extracts and analysed. Immunocytochemical analysis revealed VIP immunofluorescence apparently confined to the tegumental lining of M expansa tapeworm, a strikingly similar situation to the previously reported VIP-IR in Echinostoma liei, a parasitic cestode resident in the mouse small intestine. In mammals VIP is known to be expressed and secreted by enteric neurones and immune cells including Th2 lyrnphocytes, mast cells and oesinophils and as part of a response to antigenic and inflammatory stimulation. A Th2, mast and oesinophilic cell response is strongly characteristic of the mammalian immune response to enteric parasites. It is postulated that the VIP immunofluorescence observed on the M expansa tegumental surface in the present study may be due to VIP expressed and secreted by the host enteric neurones and / or immune cells. This possibility remains to be investigated further.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.554234  DOI: Not available
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