Characterization and localization of galanin receptors in human entorhinal cortex

Regulatory Peptides
D C DeecherE J Mufson

Abstract

The neuropeptide galanin (GAL) has a widespread distribution throughout the human cortex. The entorhinal cortex (ENT) plays a crucial role in the transfer of cortico-cortical information related to memory and displays 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 distribution and characterized GALRs using in vitro receptor autoradiography and radioligand binding assays. Autoradiograms revealed intense GALR labeling, mainly in the substantia innominata, hypothalamus, the bed nucleus of the stria terminalis and within layers 2 and 4 of the ENT. Kinetic experiments showed that saturation of GALR sites by [125I]GAL (human) (hGAL) occurred within 2 h and that this binding readily reversed in the presence of a GTP analog, but not in the presence of excess unlabeled hGAL. Analysis of [125I]hGAL binding data from saturation experiments gave KD values of 98.6+/-21.6 pM, Bmax values of 52.9+/-32.4 fmol/mg protein and identified a high and low affinity state of the GALR. The presence of 5'-guanylylimidodiphosphate (GppNHp) or NaCl reduced the agonist labeling of hGALR in ENT membranes.

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Citations

May 27, 2008·Cellular and Molecular Life Sciences : CMLS·S E CountsE J Mufson
Feb 3, 1999·Annals of the New York Academy of Sciences·B DepczynskiA Cunningham
Feb 3, 1999·Annals of the New York Academy of Sciences·E J MufsonD C Deecher
Jul 30, 2015·Expert Opinion on Therapeutic Targets·Krista FreimannÜlo Langel
Mar 10, 2004·International Review of Neurobiology·Oliver GuillinPierre Sokoloff
Jan 12, 2005·Life Sciences·Bernard Le FollPierre Sokoloff

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