Distribution and characterization of the [3H]granisetron-labelled 5-HT3 receptor in the human forebrain.
The present study has demonstrated the distribution of [3H]granisetron-labelled 5-HT3 receptors in the human forebrain with relatively high levels of this receptor in homogenates of hippocampus, caudate nucleus, putamen, nucleus accumbens and amygdala. Lower levels of 5-HT3 receptors were found in other brain regions and the cervical vagus nerve. Pharmacological characterization of the labelled 5-HT3 receptor in human putamen homogenates identified a relatively low affinity for d-tubocurarine compared to the 5-HT3 receptor in NG108-15 neuroblastoma-glioma cell homogenates. In contrast, the affinities of 19 other 5-HT3 receptor ligands were not significantly different for the [3H]granisetron-labelled receptor in these two preparations. Such findings indicate that the human putamen 5-HT3 receptor displays a unique pharmacology which may have significance given the reported clinical potential of compounds active at this receptor when assessed in animal models of disease.
Bufton
K E
KE
Department of Pharmacology, Medical School, University of Birmingham, Edgbaston, U.K.
Steward
L J
LJ
Barber
P C
PC
Barnes
N M
NM
D000368:Aged; D000369:Aged, 80 and over; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002421:Caudate Nucleus / Q000378:metabolism; D005260:Female; D017829:Granisetron / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000378:metabolism; D009928:Organ Specificity; D016548:Prosencephalon / Q000378:metabolism*; D011699:Putamen / Q000378:metabolism; D011985:Receptors, Serotonin / Q000032:analysis* / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014630:Vagus Nerve / Q000378:metabolism
D017829:Granisetron; D011985:Receptors, Serotonin