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.