Identification of 5-HT3A and 5-HT3B receptor subunits in human hippocampus

The pentameric 5-HT3 receptor complex is a ligand-gated ion channel that mediates fast synaptic transmission in the brain. Expression of two subunits (5-HT3A and 5-HT3B subunits) gives rise to at least two receptor isoforms (homomeric 5-HT3A and heteromeric 5-HT3A/3B receptors), which differ in their biophysical characteristics, although expression of these proteins has not been investigated in human brain. The expression of h5-HT3A and 5-HT3B subunits in the human hippocampus was investigated using selective polyclonal antibodies (SDS-PAGE/Western blotting, immunohistochemistry), with expression of each subunit verified by PCR detection of subunit transcripts. 5-HT3A and 5-HT3B subunit immunoreactivity was identified within the human hippocampus. The cellular pattern of expression for each subunit was similar, with predominant immunoreactivity associated with pyramidal neurones in CA fields 2 and 3, and also the relatively large neurones within the hilus (CA4 field). Transcripts for each subunit were also identified in human hippocampal tissue. These findings indicate that human hippocampal neurones are capable of forming at least two, functionally different, isoforms of the 5-HT3 receptor. Furthermore the expression pattern of 5-HT3A and 5-HT3B subunits in human hippocampus appears to differ with the rodent counterpart, which may underlie the differences in some of the behavioural effects of 5-HT3 receptor antagonists between these species. (c) 2007 Elsevier Ltd. All rights reserved.