title: Pharmacological profile of Ascaris suum ACR-16, a new homomeric nicotinic acetylcholine receptor widely distributed in Ascaris tissues.
abstract: Control of nematode parasite infections relies largely on anthelmintic drugs, several of which act on nicotinic ACh receptors (nAChRs), and there are concerns about the development of resistance. There is an urgent need for development of new compounds to overcome resistance and novel anthelmintic drug targets. We describe the functional expression and pharmacological characterization of a homomeric nAChR, ACR-16, from a nematode parasite.
  
  
  
  Using RT-PCR, molecular cloning and two-electrode voltage clamp electrophysiology, we localized acr-16 mRNA in Ascaris suum (Asu) and then cloned and expressed acr-16 cRNA in Xenopus oocytes. Sensitivity of these receptors to cholinergic anthelmintics and a range of nicotinic agonists was tested.
  
  
  
  Amino acid sequence comparison with vertebrate nAChR subunits revealed ACR-16 to be most closely related to α7 receptors, but with some striking distinctions. acr-16 mRNA was recovered from Asu somatic muscle, pharynx, ovijector, head and intestine. In electrophysiological experiments, the existing cholinergic anthelmintic agonists (morantel, levamisole, methyridine, thenium, bephenium, tribendimidine and pyrantel) did not activate Asu-ACR-16 (except for a small response to oxantel). Other nAChR agonists: nicotine, ACh, cytisine, 3-bromocytisine and epibatidine, produced robust current responses which desensitized at a rate varying with the agonists. Unlike α7, Asu-ACR-16 was insensitive to α-bungarotoxin and did not respond to genistein or other α7 positive allosteric modulators. Asu-ACR-16 had lower calcium permeability than α7 receptors.
  
  
  
  We suggest that ACR-16 has diverse tissue-dependent functions in nematode parasites and is a suitable drug target for development of novel anthelmintic compounds.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Abongwa
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Buxton
authors.affiliation: INRA, UMR Infectiologie et Santé Publique, Nouzilly, France.|Université François Rabelais de Tours, UMR Infectiologie et Santé Publique, Tours, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Courtot
authors.affiliation: INRA, UMR Infectiologie et Santé Publique, Nouzilly, France.|Université François Rabelais de Tours, UMR Infectiologie et Santé Publique, Tours, France.
authors.forename: Claude L
authors.initials: CL
authors.lastname: Charvet
authors.affiliation: INRA, UMR Infectiologie et Santé Publique, Nouzilly, France.|Université François Rabelais de Tours, UMR Infectiologie et Santé Publique, Tours, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Neveu
authors.affiliation: School of Biological Sciences, Medical Biology Centre, Queen's University Belfast, Belfast, UK.
authors.forename: Ciaran J
authors.initials: CJ
authors.lastname: McCoy
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Verma
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Robertson
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017165:Ascaris suum / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018733:Nicotinic Antagonists / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D018733:Nicotinic Antagonists; D012333:RNA, Messenger; D011978:Receptors, Nicotinic