Sequential alterations of [3H]rolipram and [3H]cyclic adenosine monophosphate binding in the gerbil brain following transient cerebral ischemia.
We examined the sequential alterations in the binding of selective cyclic adenosine monophosphate (cAMP)-phosphodiesterase (PDE) and cAMP-dependent protein kinase (cAMP-DPK) in the gerbil brain following transient cerebral ischemia using in vitro quantitative autoradiography. [3H]Rolipram, a cAMP-PDE inhibitor, and [3H]cAMP were used to label cAMP-PDE and cAMP-DPK, respectively. Gerbils were subjected to 2-min or 6-min ischemia. Two-minute ischemia, which caused no morphological neuronal damage, produced no significant changes in either [3H]rolipram or [3H]cAMP binding throughout the recirculation period. The reduction of [3H]rolipram binding in the CA1 subfield of the hippocampus began 6 h after 6-min ischemia. Seventy percent of [3H]rolipram binding was preserved at 4 days, at which time almost all CA1 pyramidal cells had been destroyed. On the other hand, the reduction of [3H]cAMP-binding sites in the CA1 subfield began 1 day after 6-min ischemia. At 4 days, 47% of [3H]cAMP-binding sites in the CA1 subfield were preserved. Furthermore, we observed a transient reduction of [3H]cAMP binding in the dentate gyrus, which is resistant to ischemia, at 1 day and 4 days. These results indicate that marked alterations of cAMP-PDE and cAMP-DPK precede neuronal death in the hippocampal CA1 subfield, and the dentate gyrus also showed a transient alteration of cAMP-DPK.
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
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Murase
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Kato
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Araki
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Kogure
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D005849:Gerbillinae; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D011494:Protein Kinases / Q000378:metabolism; D011712:Pyramidal Tracts / Q000033:anatomy & histology / Q000378:metabolism; D011760:Pyrrolidinones / Q000378:metabolism*; D020889:Rolipram; D013788:Thalamus / Q000033:anatomy & histology / Q000378:metabolism
D011760:Pyrrolidinones; D000242:Cyclic AMP; D011494:Protein Kinases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D020889:Rolipram