PHD STUDENTSHIP (INTERNALTIONAL)
A NOVEL TARGET SITES FOR ANTHELMINTICS: EFFECTS OF PF1 AND PF4 ON
ION-CHANNEL CURRENT IN MUSCLE MEMBRANES OF ASCARIS SUUM
SUPERVISOR DR. RICHARD JOHN MARTIN. DEPT. OF PRECLINICAL VET SCIENCES.
E-MAIL R.J.MARTIN. at ED.AC.UK
SUPPORTED BY PHARMACIA/UPJOHN AND VETERINARY FACULTY
Peptide receptors in parasitic nematodes have been identified as
potential sites of action for novel anthelmintics. More than 20
FMRFamide-related peptides (FaRPs) have been identified in nematodes but
the physiological effects of less than half have been described.
Two-microelectrode current clamp and patch-calmp experiments will be
used to investigated the sites of action of the FaRPs PF1 and PF4. The
aim of the experiments are to explore the properties of a novel site for
anthelmintic therapy. A PhD student will receive a training in
electrophysiological and pharmacology of nematode preparations. The
will also be trained to use the patch-clamp technique. The project is
suitabel for a motivated life sciences graduated (including
parasitology, physiology and pharmacology) and offer a training giving
good future prospects.
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PHD STUDENTSHIP
NOVEL TARGET SITES: EFFECTS OF PF1 AND PF4 ON ION-CHANNEL CURRENTS IN MUSCLE AND MUSCLE VESICLE PREPARATIONS OF ASCARIS SUUM
SUPERVISOR DR. RICHARD J. MARTIN. DEPARTMENT OF PRECLINICAL VET. SCIENCES RDSVS SUMMERHALL UNIVERSITY OF EDINBURGH. EH9 3QH
E-MAIL: R.J.MARTIN at ED.AC.UK
SUPPORTED BY PHARMACIA/UPJOHN AND VETERINARY FACULTY STUDENTSHIP.
Peptide receptors of parasitic nematodes have been identified as a potential site of action for novel anthelmintics. More than 20 FMRFamide-related peptides (FaRPs) have been identified in nematodes but the physiological effects of less than half of them have been described. All of the FaRPs so far examined increase or decrease muscle activity. They are potential new target sites for anthelmintics.
PF1
The effects of SDPNFLRFamide (PF1) on Ascaris suum muscle strips have been described. Bath-applied PF1 produces hyperpolarization with little conductance change.. PF1 receptors on Ascaris muscle has now been demonstrated (Martin and Valkanov, 1996
PF4
The effects of KPNFIRFamide (PF4) on the tone of Ascaris muscle flaps and membrane potential has been described by Maule et al. 1996. PF4 reduces the tonic and phasic contractions of muscle flaps, an effect not inhibited by N-nitro-L-arginine, a nitric oxide synthase inhibitor, suggesting that nitric oxide is not involved as a second messenger. PF4 appears to increase the Cl conductance of the muscle membrane because: 1) bath application of PF4 causes hyperpolarization and an increase in the input conductance of the muscle membrane; 2) Cl replacement converts the normal muscle relaxant effect of PF4 to that of contraction.
A two-microelectrode current clamp and patch-clamp experiments will be used to investigate the sites of action of PF1 and PF4. The aim of the experiments are to explore the properties of a novel target site for anthelmintic therapy. The Ph.D student will receive a training in electrophysiology and pharmacology of nematode preparations. They will also be trained to use the patch-clamp technique. The project is suitable for a motivated life sciences graduate and offer a training giving good future prospects.
