Endogenous reductions in N-methyl- d-aspartate receptor activity inhibit nitric oxide production in the anoxic freshwater turtle cortex

• Published in: FEBS letters 2008-05, Vol.582 (12), p.1738-1742
• Main Authors: Pamenter, Matthew Edward, Hogg, David William, Buck, Leslie Thomas
• Format: Article
• Language: English
• Subjects: 4-amino-5-methylamino-2′,7′-difluorofluorescein; Anaerobiosis; Animals; APV; Calcium; CBF; Cerebral blood flow; Cerebral Cortex - blood supply; Cerebral Cortex - metabolism; Cerebrovascular Circulation; Channel arrest; DAF-FM; Diaminofluorescein; dl-2-amino-5-phosphonopentanoic acid; ECD; excitotoxic cell death; Hypoxia; l-NAME; N G-nitro-l-arginine methyl ester; N-methyl-d-aspartate receptor; neuronal nitric oxide synthase; nitric oxide; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; nitric oxide synthase; NMDAR; nNOS; NOS; Oxygen - metabolism; Post-synaptic density 95; PSD-95; reactive oxygen species; Receptors, N-Methyl-D-Aspartate - metabolism; ROS; SNP; sodium nitroprusside dihydrate; Turtles - metabolism
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2008.04.041

Increased nitric oxide (NO) production from hypoxic mammalian neurons increases cerebral blood flow (CBF) but also glutamatergic excitotoxicity and DNA fragmentation. Anoxia-tolerant freshwater turtles have evolved NO-independent mechanisms to increase CBF; however, the mechanism(s) of NO regulation are not understood. In turtle cortex, anoxia or NMDAR blockade depressed NO production by 27 ± 3% and 41 ± 5%, respectively. NMDAR antagonists also reduced the subsequent anoxic decrease in NO by 74 ± 6%, suggesting the majority of the anoxic decrease is due to endogenous suppression of NMDAR activity. Prevention of NO-mediated damage during the transition to and from anoxia may be incidental to natural reductions of NMDAR activity in the anoxic turtle cortex.