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

Ricardo M. Zayas, Sanjive Qazi, David B. Morton, Barry A. Trimmer

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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+.

Original languageEnglish (US)
Pages (from-to)421-431
Number of pages11
JournalJournal of Neurochemistry
Volume83
Issue number2
DOIs
StatePublished - Oct 1 2002

Keywords

  • Calcium
  • Nicotinic acetylcholine receptors
  • Nitric oxide
  • Phosphodiesterase inhibitors
  • Soluble guanylyl cyclase
  • cGMP

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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