title: The action of pyrantel as an agonist and an open channel blocker at acetylcholine receptors in isolated Ascaris suum muscle vesicles.
abstract: The anthelmintic pyrantel is believed to act as an agonist at acetylcholine receptors on somatic muscle from the parasite Ascaris suum. This study aimed to confirm this mode of action of pyrantel. Single-channel recordings from muscle vesicles formed from the extrasynaptic region of the bag of somatic muscle cells of Ascaris suum were made using the patch-clamp technique. Pyrantel (0.03-100 microM) activated cation-selective channels with at least 2 conductance levels: main conductance 41 +/- 2.04 pS (mean +/- S.E., n = 28), smaller conductance 22.4 +/- 0.34 pS (mean +/- S.E., n = 8). The current/voltage plots showed a linear relationship. Detailed kinetic analysis revealed that activation of the receptor by pyrantel resulted in at least 2 distinct open and burst states and at least 3 distinct closed states. The mean open time of the channel, with 0.1 microM pyrantel, was 1.53 +/- 0.22 ms (mean +/- S.E., n = 7) at -75 mV. We have previously shown that acetylcholine activated channels with similar properties to the pyrantel-activated channels (Pennington, A.J. and R.J. Martin, 1990, J. Exp. Biol. 154, 201) confirming that pyrantel is an acetylcholine agonist. With high concentrations (100 microM) of pyrantel a sequence of rapid openings and closings of the channel was observed, indicating the presence of an open channel block. Previous experiments have shown that the anthelmintic levamisole, which also acts as an acetylcholine agonist on this preparation, induced channel block at hyperpolarised potentials with high concentrations (Robertson, S.J. and R.J. Martin, 1993, Br. J. Pharmacol. 108, 170). A comparison is made of the actions of the 3 agonists pyrantel, levamisole and acetylcholine at the nicotinic receptor in Ascaris muscle, and implications for the therapeutic use of the compounds are discussed.
authors.affiliation: University of Edinburg, Department of Preclinical Veterinary Sciences, Royal Dick School of Veterinary Sciences, Summerhall, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Robertson
authors.forename: A J
authors.initials: AJ
authors.lastname: Pennington
authors.forename: A M
authors.initials: AM
authors.lastname: Evans
authors.forename: R J
authors.initials: RJ
authors.lastname: Martin
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D017165:Ascaris suum / Q000187:drug effects*; D018679:Cholinergic Agonists; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D007978:Levamisole / Q000494:pharmacology; D009132:Muscles / Q000187:drug effects*; D011715:Pyrantel / Q000494:pharmacology*
chemical_list: D018679:Cholinergic Agonists; D007473:Ion Channels; D007978:Levamisole; D011715:Pyrantel; D000109:Acetylcholine