Nicotinic-acetylcholine receptors are functionally coupled to the nitric oxide/cGMP-pathway in insect neurons

J Neurochem. 2002 Oct;83(2):421-31. doi: 10.1046/j.1471-4159.2002.01147.x.


In addition to their ionotropic role, neuronal nicotinic acetylcholine receptors (nAChRs) can influence second messenger levels, transmitter release and gene transcription. In this study, we show that nAChRs in an insect CNS control cGMP levels by coupling to NO production. In conditions that inhibit spiking, nicotine induced cGMP synthesis. This increase in cGMP was blocked by nicotinic antagonists, and by inhibitors of both nitric oxide synthase and soluble guanylyl cyclase. The nicotinic-evoked increase in cGMP was localized to specific NO-sensitive neurons in the CNS, several of which are identified motoneurons. Because NO production requires Ca2+, we investigated the effect of nicotinic stimulation on [Ca2+]i in cultured neurons. We found that activation of nAChRs increased [Ca2+]i, which was blocked by nAChR antagonists. Nicotinic stimulation of neurons in the isolated CNS in low-Na+, also evoked increases in [Ca2+]i independent of fast changes in voltage. In addition, approximately 10% of the nicotinic-evoked [Ca2+]i increase in cultured neurons persisted when voltage-gated Ca2+ channels were blocked by Ni2+. Under the same conditions, nicotinic stimulation of cGMP in the CNS was unaffected. These combined results suggest that nicotinic stimulation is coupled to NOS potentially by directly gating Ca2+.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Calcium / metabolism
  • Cells, Cultured
  • Cyclic GMP / metabolism*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Guanylate Cyclase
  • In Vitro Techniques
  • Larva
  • Manduca
  • Nervous System / cytology
  • Nervous System / drug effects
  • Nervous System / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nickel / pharmacology
  • Nicotine / pharmacology
  • Nicotinic Agonists / pharmacology
  • Nicotinic Antagonists / pharmacology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Soluble Guanylyl Cyclase


  • Enzyme Inhibitors
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Nitric Oxide Donors
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Nicotinic
  • Nitric Oxide
  • Nicotine
  • Nickel
  • Nitric Oxide Synthase
  • Guanylate Cyclase
  • Soluble Guanylyl Cyclase
  • Cyclic GMP
  • Calcium