Rapid Reduction in [3H]Prazosin Binding to Gerbil Forebrain Membranes during Bilateral Common Carotid Artery Occlusion

Transient cerebral ischemia results in selective neuronal cell death. The mechanisms underlying this selective vulnerability to ischemia are only beginning to be elucidated. We studied the effect of ischemia on α 1 -adrenergic receptor binding by measuring [ 3 H]prazosin binding in gerbil forebrain membranes after 10 min of bilateral carotid occlusion. Binding was reduced from 62 ± 3 to 33 ± 4 fmol/mg protein. Binding in the same membranes to β 2 -adrenergic receptors were also decreased, but not to the extent of that to β 1 -adrenergic receptors. Binding to muscarinic cholinergic ([ 3 H]quinuclydil benzilate) and β 1 -adrenergic receptors were only slightly depressed. Surprisingly, the protein content was significantly increased in the membrane fraction studied from ischemic forebrain (68 ± 4 mg/g wet weight) compared with sham operated controls (57 ± 4). The dramatic decrease in α 1 -adrenergic receptor binding during ischemia is consistent with receptor binding studies of membranes pretreated with phospholipase A 2 in vitro. It is not clear what effect this change in α 1 -adrenergic receptor binding has on subsequent selective neuronal death. The recent demonstration that catecholamines and locus ceruleus neurons influence the loss of CA 1 neurons in the hippocampus suggests that it may play an important modulatory role.