TY - JOUR
T1 - Nicotinic-acetylcholine receptors are functionally coupled to the nitric oxide/cGMP-pathway in insect neurons
AU - Zayas, Ricardo M.
AU - Qazi, Sanjive
AU - Morton, David B.
AU - Trimmer, Barry A.
PY - 2002/10
Y1 - 2002/10
N2 - 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+.
AB - 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+.
KW - Calcium
KW - Nicotinic acetylcholine receptors
KW - Nitric oxide
KW - Phosphodiesterase inhibitors
KW - Soluble guanylyl cyclase
KW - cGMP
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U2 - 10.1046/j.1471-4159.2002.01147.x
DO - 10.1046/j.1471-4159.2002.01147.x
M3 - Article
C2 - 12423252
AN - SCOPUS:0036798435
SN - 0022-3042
VL - 83
SP - 421
EP - 431
JO - Journal of neurochemistry
JF - Journal of neurochemistry
IS - 2
ER -