Mechanisms of M(1) muscarinic receptor-mediated up-regulation of neuronal nitric oxide synthase in N1E-115 neuroblastoma cells.
The neuronal form of nitric oxide synthase (nNOS) was generally assumed to be constitutively expressed at a constant level. However, it is now becoming recognized that its expression can be modulated by a number of physiological and pathophysiological conditions. Previously, we reported that nNOS expression is up-regulated after prolonged muscarinic M(1) receptor stimulation. In this work, we report that muscarinic receptor activation signals the up-regulation of nNOS via multiple pathways in N1E-115 mouse neuroblastoma cells. These include protein kinase C (PKC) activation, cytosolic calcium mobilization and NO production. Further characterization showed that the half-life of nNOS is slightly, but significantly, increased in agonist-pretreated cells compared with vehicle-treated control cells. Based on these data, it appears that the level of nNOS expression is modulated in a complex manner by a number of mechanisms that include, but might not be limited to, those described here.
Cuadra
Adolfo E
AE
NUMS, Dept. of Neurology, Northwestern University, Chicago, IL, USA.
El-Fakahany
Esam E
EE
D000704:Analysis of Variance; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D002217:Carbachol / Q000494:pharmacology; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009447:Neuroblastoma / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D043643:Receptor, Muscarinic M1 / Q000502:physiology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D002614:Chelating Agents; D018679:Cholinergic Agonists; D004791:Enzyme Inhibitors; D007476:Ionophores; D018727:Muscarinic Antagonists; D009419:Nerve Tissue Proteins; D010703:Phorbol Esters; D043643:Receptor, Muscarinic M1; C119222:phorbol-12-myristate; D015240:Phorbol 12,13-Dibutyrate; D004533:Egtazic Acid; D015759:Ionomycin; D001285:Atropine; D002217:Carbachol; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid