Characterization of GAR-2, a novel G protein-linked acetylcholine receptor from Caenorhabditis elegans

J Neurochem. 2000 Nov;75(5):1800-9. doi: 10.1046/j.1471-4159.2000.0751800.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Base Sequence
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism
  • Cholinergic Agonists / pharmacology
  • Cholinergic Antagonists / pharmacology
  • Cloning, Molecular
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • GTP-Binding Proteins / metabolism*
  • Gene Expression
  • Microinjections
  • Molecular Sequence Data
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Phylogeny
  • Potassium Channels / drug effects
  • Potassium Channels / genetics
  • Potassium Channels / metabolism
  • Potassium Channels, Inwardly Rectifying*
  • Receptors, Cholinergic / chemistry
  • Receptors, Cholinergic / genetics*
  • Receptors, Cholinergic / metabolism
  • Receptors, Muscarinic / genetics
  • Receptors, Muscarinic / metabolism
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Xenopus


  • Cholinergic Agonists
  • Cholinergic Antagonists
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • G protein-linked acetylcholine receptor 2
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Cholinergic
  • Receptors, Muscarinic
  • GTP-Binding Proteins
  • Acetylcholine

Associated data

  • GENBANK/AF272738