Norepinephrine increases cyclic GMP levels in cerebellar cells from neuronal nitric oxide synthase knockout mice.
Cyclic GMP is an important intracellular messenger in the nervous system that may mediate cellular forms of neuronal plasticity. Previous studies show that most neurotransmitters stimulate cyclic GMP levels by the activation of nitric oxide synthase (NOS). In this study, we report that in primary cell cultures from the cerebellum of neuronal NOS knockout mice, norepinephrine stimulates an increase in cyclic GMP content. This increase is seen in both granule cell and astrocyte cultures and is not blocked by inhibitors of NOS or by inhibition of soluble guanylyl cyclase. These results suggest a novel pathway by which norepinephrine enhances cyclic GMP levels in the nervous system.
Morton
D B
DB
Department of Biological Structure and Function, School of Dentistry, Oregon Health Sciences University, Portland 97201, USA.
Bredt
D S
DS
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology; D002531:Cerebellum / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052248:Nitric Oxide Synthase Type I; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D013565:Sympatholytics / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D010069:Oxadiazoles; D011810:Quinoxalines; D013565:Sympatholytics; D013566:Sympathomimetics; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D009638:Norepinephrine; D011224:Prazosin