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 α1-adrenergic receptor binding by measuring [3H]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 β2-adrenergic receptors were also decreased, but not to the extent of that to β1-adrenergic receptors. Binding to muscarinic cholinergic ([3H]quinuclydil benzilate) and β1-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 α1-adrenergic receptor binding during ischemia is consistent with receptor binding studies of membranes pretreated with phospholipase A2 in vitro. It is not clear what effect this change in α1-adrenergic receptor binding has on subsequent selective neuronal death. The recent demonstration that catecholamines and locus ceruleus neurons influence the loss of CA1 neurons in the hippocampus suggests that it may play an important modulatory role.
Nuclear Compartmentalization of α1-Adrenergic Receptor Signaling in Adult Cardiac Myocytes