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Biexponential Kinetics of (R)‐α‐[ 3 H]Methylhistamine Binding to the Rat Brain H 3 Histamine Receptor
Author(s) -
West Robert E.,
Zweig Adam,
Granzow Russell T.,
Siegel Marvin I.,
Egan Robert W.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb04946.x
Subject(s) - dimaprit , histamine h3 receptor , thioperamide , agonist , chemistry , histamine , histamine receptor , medicine , histamine h2 receptor , endocrinology , receptor , biology , biochemistry , antagonist
The H 3 histamine receptor is a high‐affinity receptor reported to mediate inhibition of CNS histidine decarboxylase activity and depolarization‐induced histamine release. We have used ( R )‐α‐[ 3 H]methylhistamine, a specific, high‐affinity agonist, to characterize ligand binding to this receptor. Saturation binding studies with rat brain membranes disclosed a single class of sites ( K D = 0.68 n M; B max = 78 fmol/mg of protein). Competition binding assays also yielded an apparently single class of sites with a rank order of potency for ligands characteristic of an H 3 histamine receptor: N α ‐methylhistamine, ( R )‐α‐methylhistamine > histamine, thioperamide > impromidine > burimamide > dimaprit. In contrast, kinetic studies disclosed two classes of sites, one with fast, the other with slow on‐and‐off rates. Density of ( R )‐α‐[ 3 H]methylhistamine binding followed the order: caudate, midbrain (thalamus and hippocampus), cortex > hypothalamus > brainstem > cerebellum. These data are consistent with an H 3 histamine receptor, distinct from H 1 and H 2 receptors, that occurs in two conformations with respect to agonist association and dissociation or with multiple H 3 receptor subtypes that are at present pharmacologically undif‐ferentiated.