title: Characterization of GAR-2, a novel G protein-linked acetylcholine receptor from Caenorhabditis elegans.
abstract: We have previously identified two G protein-linked acetylcholine receptors (GARs), GAR-1 and GAR-3, in the nematode Caenorhabditis elegans. Whereas GAR-3 is a homologue of muscarinic acetylcholine receptors (mAChRs), GAR-1 is similar to but pharmacologically distinct from mAChRs. In the current work we isolated a new type of GAR using C. elegans genome sequence information. This receptor, named GAR-2, consists of 614 amino acid residues and has seven putative transmembrane domains. Database searches indicate that GAR-2 is most similar to GAR-1 and closely related to GAR-3/mAChRs. The overall amino acid sequence identities to GAR-1 and GAR-3 are approximately 32 and approximately 23%, respectively. When GAR-2 was coexpressed with the G protein-activated inwardly rectifying K(+) (GIRK1) channel in Xenopus oocytes, acetylcholine was able to evoke the GIRK current in a dose-dependent fashion. Oxotremorine, a classical muscarinic agonist, had little effect on the receptor, indicating that GAR-2 is pharmacologically different from mAChRs but rather similar to GAR-1. GAR-2 differs from GAR-1, however, in that it showed virtually no response to muscarinic antagonists such as atropine, scopolamine, and pirenzepine. Expression studies using green fluorescent protein reporter gene fusion revealed that GAR-2 is expressed in a subset of C. elegans neurons, distinct from those expressing GAR-1. Together with our previous reports, this study demonstrates that diverse types of GARs are present in C. elegans.
authors.affiliation: Molecular Neurobiology Laboratory, Institute of Molecular Biology and Genetics, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea.
authors.forename: Y S
authors.initials: YS
authors.lastname: Lee
authors.forename: Y S
authors.initials: YS
authors.lastname: Park
authors.forename: S
authors.initials: S
authors.lastname: Nam
authors.forename: S J
authors.initials: SJ
authors.lastname: Suh
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: B K
authors.initials: BK
authors.lastname: Kaang
authors.forename: N J
authors.initials: NJ
authors.lastname: Cho
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D018679:Cholinergic Agonists / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003001:Cloning, Molecular; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015870:Gene Expression; D008845:Microinjections; D008969:Molecular Sequence Data; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010802:Phylogeny; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
chemical_list: D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C415370:G protein-linked acetylcholine receptor 2; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins; D000109:Acetylcholine