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Nicotinic‐acetylcholine receptors are functionally coupled to the nitric oxide/cGMP‐pathway in insect neurons
Author(s) -
Zayas Ricardo M.,
Qazi Sanjive,
Morton David B.,
Trimmer Barry A.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01147.x
Subject(s) - nicotinic agonist , ionotropic effect , stimulation , ganglion type nicotinic receptor , acetylcholine , chemistry , alpha 4 beta 2 nicotinic receptor , nicotinic antagonist , acetylcholine receptor , nitric oxide , soluble guanylyl cyclase , receptor , endocrinology , biology , nicotinic acetylcholine receptor , medicine , biochemistry , glutamate receptor , guanylate cyclase
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 Ca 2+ , we investigated the effect of nicotinic stimulation on [Ca 2+ ] i in cultured neurons. We found that activation of nAChRs increased [Ca 2+ ] i , which was blocked by nAChR antagonists. Nicotinic stimulation of neurons in the isolated CNS in low‐Na + , also evoked increases in [Ca 2+ ] i independent of fast changes in voltage. In addition, approximately 10% of the nicotinic‐evoked [Ca 2+ ] i increase in cultured neurons persisted when voltage‐gated Ca 2+ channels were blocked by Ni 2+ . 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 Ca 2+ .