Neurophysiology of glutamatergic signalling and anthelmintic action in Ascaris suum: pharmacological evidence for a kainate receptor.
Electrophysiological and pharmacological techniques were used to study glutamatergic signalling in the parasitic nematode, Ascaris suum. Glutamate or kainate injections into whole worms produced a paralysed quasi-static posture similar to the waveform in behaving worms. The DE2 motorneuron class is a primary target. Several glutamatergic substances produced pronounced conductance increases and depolarization in DE2; domoate and kainate were the most potent agonists tested. Glutamate responses and spontaneous excitatory post-synaptic potentials in DE2 were reversibly blocked in sodium-free saline. DE2 sensitivity to exogenous glutamate was sustained during block of synaptic transmission suggesting that glutamatergic receptors are located on DE2 neurons. The glutamate-induced response was localized to the DE2 dendrite, coincident with the synapses responsible for spontaneous potentials in DE2. Steady-state potentials reached during glutamate superfusion were similar to the reversal potentials for both the spontaneous post-synaptic potentials and glutamate, also suggesting that these potentials may be glutamatergic. Non-N-methyl-D-aspartate receptor antagonists partially blocked spontaneous DE2 excitatory potentials and responses elicited by exogenous glutamate and kainate. This glutamatergic pathway may play a role in nematode locomotory behaviour and account for the paralysing anthelmintic action of excitatory amino acid analogues like kainate and domoate.
Davis
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RE
Department of Zoology, University of Wisconsin-Madison 53706, USA. redavis@facstaff.wisc.edu
D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology*; D017165:Ascaris suum / Q000187:drug effects / Q000502:physiology*; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology*; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000502:physiology; D018092:Kainic Acid Receptors / Q000502:physiology*; D015398:Signal Transduction
D000969:Antinematodal Agents; D018690:Excitatory Amino Acid Agonists; D018698:Glutamic Acid; D007608:Kainic Acid; D009467:Neuromuscular Depolarizing Agents; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; C012301:domoic acid