Campus Units
Biomedical Sciences
Document Type
Article
Publication Version
Accepted Manuscript
Publication Date
9-2009
Journal or Book Title
International Journal for Parasitology
Volume
39
Issue
11
First Page
1215
Last Page
1222
DOI
10.1016/j.ijpara.2009.03.001
Abstract
Acetylcholine (ACh) is a neurotransmitter/neuromodulator in the nematode nervous system and induces its effects through interaction with both ligand-gated ion channels (LGICs) and G protein-coupled receptors (GPCRs). The structure, pharmacology and physiological importance of LGICs have been appreciably elucidated in model nematodes, including parasitic species where they are targets for anthelmintic drugs. Significantly less, however, is understood about nematode ACh GPCRs, termed GARs (G protein-linked ACh receptors). What is known comes from the free-livingCaenorhabditis elegans as no GARs have been characterized from parasitic species. Here we clone a putative GAR from the pig gastrointestinal nematode Ascaris suum with high structural homology to the C. elegans receptor GAR-1. Our GPCR, dubbed AsGAR-1, is alternatively spliced and expressed in the head and tail of adult worms but not in dorsal or ventral body wall muscle, or the ovijector. ACh activated AsGAR-1 in a concentration-dependent manner but the receptor was not activated by other small neurotransmitters. The classical muscarinic agonists carbachol, arecoline, oxotremorine M and bethanechol were also AsGAR-1 agonists but pilocarpine was ineffective. AsGAR-1 activation by ACh was partially antagonized by the muscarinic blocker atropine but pirenzepine and scopolamine were largely ineffective. Certain biogenic amine GPCR antagonists were also found to block AsGAR-1. Our conclusion is that Ascaris possesses G protein-coupled ACh receptors that are homologous in structure to those present in C. elegans, and that although they have some sequence homology to vertebrate muscarinic receptors, their pharmacology is atypically muscarinic.
Copyright Owner
Australian Society for Parasitology Inc.
Copyright Date
2009
Language
en
File Format
application/pdf
Recommended Citation
Kimber, Michael J.; Sayegh, Laura; El-Shehabi, Fouad; Song, Chuanzhe; Zamanian, Mostafa; Woods, Debra J.; Day, Timothy A.; and Ribeiro, Paula, "Identification of an Ascaris G protein-coupled acetylcholine receptor with atypical muscarinic pharmacology" (2009). Biomedical Sciences Publications. 22.
https://lib.dr.iastate.edu/bms_pubs/22
Comments
This article is from International Journal for Parasitology 39 (2009): 1215–1222, doi:10.1016/j.ijpara.2009.03.001. Posted with permission.