Autoradiographic analysis of second messenger and neurotransmitter system receptors in the gerbil hippocampus following transient forebrain ischemia.
Changes in second messenger and neurotransmitter system receptor ligand binding induced by transient forebrain ischemia were studied in the gerbil hippocampus. The animals were allowed variable periods of recovery ranging from 2 h to 7 days after 5-min bilateral carotid artery occlusion. The binding of second messenger systems ([3H]inositol 1,4,5-trisphosphate ([3H]IP3)to inositol 1,4,5-triphosphate, [3H]forskolin to adenylate cyclase and [3H]phorbol 12,13-dibutylate to protein kinase C) and neurotransmitter receptor systems ([3H]PN200-110 to L-type calcium channels. [3H]N6-cyclohexyl-adenosine to adenosine A1 and [3H]quinuclidinyl benzilate to muscarinic cholinergic receptor) were assayed using quantitative autoradiography. In the CA1 subfield, 2 h after ischemia, [3H]IP3, [3H]forskolin, and [3H]quinuclidinyl benzilate binding activities significantly decreased by 25, 17 and 13%, respectively, though no morphological abnormalities were obvious. Six hours after ischemia, the [3H]phorbol 12,13-dibutylate binding activity in the stratum oriens of the CA1 subfield increased by 15%. One day after ischemia, [3H]PN200-110 binding activity in this subfield decreased by 26%, and 7 days after ischemia, [3H]phorbol 12,13-dibutylate and [3H]N6-cyclohexyl-adenosine receptor binding activities decreased in this subfield. In particular, at 7 days after ischemia, [3H]IP3 binding activity in the CA1 subfield showed a complete decline. In the CA3 subfield, [3H]PN200-110 binding activity decreased 2 days after ischemia, and [3H]IP3 and [3H]N6-cyclohexyl-adenosine binding activities decreased 7 days after ischemia. In the dentate gyrus, the structure of which remained histologically intact after ischemic insult, [3H]IP3 and [3H]forskolin binding activities decreased 7 days after ischemia. In contrast, the [3H]phorbol 12,13-dibutylate binding activity increased in the molecular layer of the dentate gyrus 7 days after ischemia. These results indicate that marked alteration of intracellular signal transduction precedes neuronal damage in the hippocampal CA1 subfield and that the histologically intact CA3 and dentate gyrus also shows modulated neuronal transmission after ischemia.
Hara
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Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Onodera
H
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Kato
H
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Araki
T
T
Kogure
K
K
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D017275:Isradipine; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D010069:Oxadiazoles / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D011712:Pyramidal Tracts / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism*; D015290:Second Messenger Systems; D013997:Time Factors; D014316:Tritium
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010069:Oxadiazoles; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D011976:Receptors, Muscarinic; D011983:Receptors, Purinergic; D014316:Tritium; D005576:Colforsin; C027513:N(6)-cyclohexyladenosine; D015240:Phorbol 12,13-Dibutyrate; D011813:Quinuclidinyl Benzilate; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D000241:Adenosine; D017275:Isradipine