Cloning and Expression of a G Protein‐Linked Acetylcholine Receptor from Caenorhabditis elegans

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Abstract
: We have isolated a cDNA clone from the nematode Caenorhabditis elegans that encodes a protein of greatest sequence similarity to muscarinic acetylcholine receptors. This gene codes for a polypeptide of 682 amino acids containing seven putative transmembrane domains. The amino acid identities, excluding a highly variable middle portion of the third intracellular loop, to the human m1‐m5 receptors are 28‐34%. When this cloned receptor was coexpressed with a G protein‐gated inwardly rectifying K+ channel (GIRK1) in Xenopus oocyte, acetylcholine was able to elicit the GIRK current. This acetylcholine‐induced current was substantially inhibited by the muscarinic antagonist atropine in a reversible manner. However, another muscarinic agonist oxotremorine and antagonists scopolamine and pirenzepine had little or negligible effects on this receptor. Taken together, these results suggest that the cloned gene encodes a G protein‐linked acetylcholine receptor that is most similar to but pharmacologically distinct from muscarinic acetylcholine receptors.