title: A common muscarinic pathway for diapause recovery in the distantly related nematode species Caenorhabditis elegans and Ancylostoma caninum.
abstract: Converging TGF-beta and insulin-like neuroendocrine signaling pathways regulate whether Caenorhabditis elegans develops reproductively or arrests at the dauer larval stage. We examined whether neurotransmitters act in the dauer entry or recovery pathways. Muscarinic agonists promote recovery from dauer arrest induced by pheromone as well as by mutations in the TGF-beta pathway. Dauer recovery in these animals is inhibited by the muscarinic antagonist atropine. Muscarinic agonists do not induce dauer recovery of either daf-2 or age-1 mutant animals, which have defects in the insulin-like signaling pathway. These data suggest that a metabotropic acetylcholine signaling pathway activates an insulin-like signal during C. elegans dauer recovery. Analogous and perhaps homologous cholinergic regulation of mammalian insulin release by the autonomic nervous system has been noted. In the parasitic nematode Ancylostoma caninum, the dauer larval stage is the infective stage, and recovery to the reproductive stage normally is induced by host factors. Muscarinic agonists also induce and atropine potently inhibits in vitro recovery of A. caninum dauer arrest. We suggest that host or parasite insulin-like signals may regulate recovery of A. caninum and could be potential targets for antihelminthic drugs.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Building 68-289, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Tissenbaum
authors.forename: J
authors.initials: J
authors.lastname: Hawdon
authors.forename: M
authors.initials: M
authors.lastname: Perregaux
authors.forename: P
authors.initials: P
authors.lastname: Hotez
authors.forename: L
authors.initials: L
authors.lastname: Guarente
authors.forename: G
authors.initials: G
authors.lastname: Ruvkun
mesh_terms: D000722:Ancylostoma / Q000378:metabolism*; D000723:Ancylostomatoidea / Q000378:metabolism; D000818:Animals; D001115:Arecoline / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007814:Larva / Q000378:metabolism*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000819:agonists / Q000037:antagonists & inhibitors; D010095:Oxotremorine / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D007328:Insulin; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010862:Pilocarpine; D001115:Arecoline; D010095:Oxotremorine; D001285:Atropine; C075027:diapause hormone