{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:47:48Z","timestamp":1790761668434,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,5,12]],"date-time":"2016-05-12T00:00:00Z","timestamp":1463011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Insect neurosecretory cells, called dorsal unpaired median neurons, are known to express two \u03b1\u2010bungarotoxin\u2010insensitive nicotinic acetylcholine receptor (nAChR) subtypes, nAChR1 and nAChR2. It was demonstrated that nAChR1 was sensitive to cAMP\/cAMP\u2010dependent protein kinase (PKA) regulation, resulting in a modulation of nicotine currents. In this study, we show that cyclic guanosine monophosphate (cGMP)\/cGMP\u2010dependent protein kinase (PKG) pathway modulates nicotine\u2010induced currents, as increased cGMP affects the second compound of the biphasic current\u2013voltage curve, corresponding to the nAChR2 receptors. Indeed, maintaining the guanosine triphosphate level with 100\u00a0\u03bcM guanosine triphosphate\u2010\u03b3\u2010S increased nicotine currents through nAChR2. We also\u00a0demonstrated that inhibition of PKG activity with 0.2\u00a0\u03bcM (8R,9S,11S)\u2010(\u2010)\u20109\u2010methoxy\u2010carbamyl\u20108\u2010methyl\u20102,3,9,10\u2010tetrahydro\u20108,11\u2010epoxy\u20101H,8H,11H\u20102,7b,11a\u2010trizadibenzo\u2010(a,g)\u2010cycloocta\u2010(c,d,e)\u2010trinden\u20101\u2010one (KT5823), a PKG specific inhibitor, reduced nicotine\u2010induced current amplitudes. KT5823 effect on nicotine currents is associated with calcium (Ca<jats:sup>2+<\/jats:sup>) activity because inhibition of Ca<jats:sup>2+<\/jats:sup> concentration with cadmium chloride (CdCl<jats:sub>2<\/jats:sub>) abolished KT5823\u2010induced inhibition mediated by nAChR2. However, specific inhibition of nitric oxide\u2010guanylyl cyclase (GC) complex by 10\u00a0\u03bcM 1H\u2010[1,2,4]oxadiazolo[4,3\u2010a]quinoxalin\u20101\u2010one (ODQ) significantly increased nicotine\u2010induced current amplitudes on both nAChR1 and nAChR2. These results suggest that nicotine\u2010induced currents mediated by both \u03b1\u2010bungarotoxin\u2010insensitive nAChR1 and nAChR2 are coupled to the cGMP\/PKG pathway.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13633-fig-0010-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>We propose that nicotinic acetylcholine receptor activation induces an increase in intracellular calcium (Ca<jats:sup>2+<\/jats:sup>) concentration. Elevation of intracellular Ca<jats:sup>2+<\/jats:sup> results in the formation of Ca<jats:sup>2+<\/jats:sup>\u2010calmodulin (CaM) complex, which activates guanylyl cyclase (GC) and\/or adenylyl cyclase (AC). Ca<jats:sup>2+<\/jats:sup>\u2010CaM complex could activate Ca<jats:sup>2+<\/jats:sup> calmodulin kinase II which could directly or indirectly modulate the nicotinic response. The mechanisms by which cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) interact remain unclear. We demonstrate that nicotine\u2010induced currents are coupled to the cGMP\/PKG pathway.\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13633","type":"journal-article","created":{"date-parts":[[2016,4,10]],"date-time":"2016-04-10T12:34:28Z","timestamp":1460291668000},"page":"931-938","source":"Crossref","is-referenced-by-count":13,"title":["cGMP\/cGMP\u2010dependent protein kinase pathway modulates nicotine\u2010induced currents through the activation of \u03b1\u2010bungarotoxin\u2010insensitive nicotinic acetylcholine receptors from insect neurosecretory cells"],"prefix":"10.1111","volume":"137","author":[{"given":"Safa","family":"Mannai","sequence":"first","affiliation":[{"name":"Universit\u00e9 d'Orl\u00e9ans Laboratoire de Biologie des Ligneux et des Grandes Cultures (LBLGC) UPRES EA, Rue de Chartres Orl\u00e9ans France"},{"name":"Universit\u00e9 de Tunis El Manar Facult\u00e9 des Sciences Campus Universitaire Farhat Hached Rommana Tunis Tunisie"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lofti","family":"Bitri","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tunis El Manar Facult\u00e9 des Sciences Campus Universitaire Farhat Hached Rommana Tunis Tunisie"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steeve H.","family":"Thany","sequence":"additional","affiliation":[{"name":"Universit\u00e9 d'Orl\u00e9ans Laboratoire de Biologie des Ligneux et des Grandes Cultures (LBLGC) UPRES EA, Rue de Chartres Orl\u00e9ans France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91147-S"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2013.04.011"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00784.2011"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00196.2009"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.60.1.80"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02644.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.505807"},{"key":"e_1_2_7_9_1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1242\/jeb.144.1.535","article-title":"Ionic species involved in the electrical activity of single adult aminergic neurones isolated from the sixth abdominal ganglion of the cockroach Periplaneta americana","volume":"144","author":"Lapied B.","year":"1989","journal-title":"J. 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