Premium
Identification and Characterisation of 5‐Hydroxytryptamine 3 Recognition Sites in Human Brain Tissue
Author(s) -
Barnes J. M.,
Barnes N. M.,
Costall B.,
Ironside J. W.,
Naylor R. J.
Publication year - 1989
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.1471-4159.1989.tb09244.x
Subject(s) - receptor , human brain , binding site , hippocampal formation , hippocampus , population , endocrinology , medicine , amygdala , serotonin , chemistry , 5 ht receptor , biology , biophysics , biochemistry , neuroscience , environmental health
[ 3 H]Zacopride displayed regional saturable specific binding to homogenates of human brain tissues, as defined by the inclusion of BRL43694 [ endo‐N ‐(9‐methyl‐9‐azabicyclo[3.3.1]non‐3‐yl)‐l‐methylindazole‐3‐carboxamide] in the incubation media. Scatchard analysis of the saturation data obtained from amygdaloid and hippocampal tissues identified the binding as being of high affinity and to a homogeneous population of binding sites ( K D = 2.64 ± 0.75 and 2.93 ± 0.41 nmol/L and B max = 55 ± 7 and 44 ± 9 fmol/ mg of protein in the amygdala and hippocampus, respectively). 5‐Hydroxytryptamine 3 (5‐HT 3 ) receptor agonists and antagonists competed for the [ 3 H]zacopride binding site, competing with up to 40% of total binding with a similar rank order of affinity in both tissues; agents acting on various other neurotransmitter receptors failed to inhibit binding. Kinetic data revealed a fast association that was fully reversible (k +1 = 6.61 × 10 5 and 7.65 × 10 5 /mol/L/s and k ‐1 = 3.68 × 10 −3 and 3.45 × 10 −3 /s in the amygdala and hippocampus, respectively). It is concluded that [ 3 H]zacopride selectively labels with high affinity 5‐HT 3 recognition sites in human amygdala and hippocampus and, if these binding domains represent 5‐HT 3 receptors, may provide the opportunity for 5‐HT 3 receptor antagonists to modify 5‐HT function in the human brain