CHARACTERIZATION AND LOCALIZATION OF GALANIN RECEPTORS IN HUMAN ENTORHINAL CORTEX

The neuropeptide galanin (GAL) has a widespread distribution throughou t the human cortex. The entorhinal cortex (ENT) plays a crucial role i n the transfer of cortico-cortical information related to memory and d isplays severe degeneration in Alzheimer's disease (AD). However, very little is known about the pharmacology of the GAL receptor (GALR) in normal human ENT. Therefore, we pharmacologically visualized their dis tribution and characterized GALRs using in vitro receptor autoradiogra phy and radioligand binding assays. Autoradiograms revealed intense GA LR labeling, mainly in the substantia innominata, hypothalamus, the be d nucleus of the stria Its terminalis and within layers 2 and 4 of the ENT. Kinetic experiments showed that saturation of GALR sites by [I-1 25]GAL (human) (hGAL) occurred within 2 h and that this binding readil y reversed in the presence of a GTP analog, but not in the presence of excess unlabeled hGAL. Analysis of [I-125]hGAL binding data from satu ration experiments gave K-D values of 98.6+/-21.6 pM, B-max values of 52.9+/-32.4 fmol/mg protein and identified a high and low affinity sta te of the GALR. The presence of 5'-guanylylimidodiphosphate (GppNHp) o r NaCl reduced the agonist labeling of hGALR in ENT membranes. (C) 199 8 Elsevier Science B.V.