In vivo exposure to carbon monoxide causes delayed impairment of activation of soluble guanylate cyclase by nitric oxide in rat brain cortex and cerebellum.
Carbon monoxide induces delayed neurological and neuropathological alterations, including memory loss and cognitive impairment. The bases for the delay remain unknown. Activation of soluble guanylate cyclase by nitric oxide modulates some forms of learning and memory. Carbon monoxide binds to soluble guanylate cyclase, activating it but interfering with its activation by nitric oxide. The aim of this work was to assess whether exposure of rats to carbon monoxide alters the activity of soluble guanylate cyclase or its modulation by nitric oxide in cerebellum or cerebral cortex. Rats exposed chronically or acutely to carbon monoxide were killed 24 h or 7 days later. Acute carbon monoxide exposure decreased cyclic guanosine monophosphate (cGMP) content and reduced activation of soluble guanylate cyclase by nitric oxide. Cortex was more sensitive than cerebellum to chronic exposure, which reduced activation of soluble guanylate cyclase by nitric oxide in cortex. In cerebellum, chronic exposure induced delayed impairment of soluble guanylate cyclase activation by nitric oxide. Acute exposure effects were also stronger at 7 days than at 24 h after exposure. This delayed impaired modulation of soluble guanylate cyclase by nitric oxide may contribute to delayed memory loss and cognitive impairment in humans exposed to carbon monoxide.
Hernández-Viadel
Mariluz
M
Laboratory of Neurobiology, Fundación Valenciana de Investigaciones Biomédicas, Amadeo de Saboya 4, 46010 Valencia, Spain.
Castoldi
Anna F
AF
Coccini
Teresa
T
Manzo
Luigi
L
Erceg
Slaven
S
Felipo
Vicente
V
D000818:Animals; D002248:Carbon Monoxide / Q000633:toxicity*; D002531:Cerebellum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D021122:Protein Subunits / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D013997:Time Factors
D021122:Protein Subunits; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D002248:Carbon Monoxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP