CALCIUM-ANTAGONIST, ADENOSINE-A1, AND MUSCARINIC BINDINGS IN RAT HIPPOCAMPUS AFTER TRANSIENT ISCHEMIA

The protective roles of Ca2+ channel blockers against ischemic hippocampal damage are still debated. We used autoradiography to study postischemic L-type Ca2+ channels (1, 4-dihydropyridine Ca2+ channel blocker binding), adenosine A, receptors, and muscarinic chollnergic receptors in the rat hippocampus using [3H]PN200-110 (PN), [3H]cyclo-hexyladenosine (CHA), and [3H]quinuclidinyl benzilate (QNB), respectively, in 49 rats subjected to 20 minutes of forebrain ischemia. The rats were decapitated after 1 (n=7), 3 (n=7), 6 (n=8), 12 (n=7), 24 (n=6), 48 (n=6), or 168 (n=8) hours of recirculation; eight control rats were sham-operated but experienced no cerebral ischemia. Reduced receptor binding preceding the delayed death of CAl pyramidal cells was first observed in the stratum oriens of the CAl subfield. Significant reductions in [3H]PN, [3H]CHA, and [3H]QNB bindings of this stratum compared with control were noticed after 3 (35%, p<0.01), 12 (31%, p<0.01), and 1 (10%, p<0.05)hours of recirculation, respectively. By 168 hours after ischemia (when the populations of CAl pyramidal cells were depleted) all strata in the CAl subfield had lost most of their receptor sites, and [3H]PN, [3H]CHA, and [3H]QNB bindings in the stratum oriens were decreased to 23%, 30%, and 63% of control (p<0.01). Although [3H]PN binding in the CA3 subfield did not change significantly during 168 hours after ischemia, the histologically intact dentate gyrus exhibited a 31% loss of binding sites compared with control (p<0.05). These results indicate predominant localization of Ca2+ antagonist binding sites on the CAl pyramidal cells. The reduction in [3H]PN binding early during reperfusion may explain the contradictory results regarding the protective role of Ca2+ channel blockers against CAl pyramidal cell death. Postischemic administration of Ca2+ antagonists may be much less effective than preischemic administration. © 1990 American Heart Association, Inc.