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The pentameric 5-HT(3) receptor complex is a ligand-gated ion channel that mediates fast synaptic transmission in the brain. Expression of two subunits (5-HT(3A) and 5-HT(3B) subunits) gives rise to at least two receptor isoforms (homomeric 5-HT(3A) and heteromeric 5-HT(3A/3B) receptors), which differ in their biophysical characteristics, although expression of these proteins has not been investigated in human brain. The expression of h5-HT(3A) and 5-HT(3B) 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-HT(3A) and 5-HT(3B) 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-HT(3) receptor. Furthermore the expression pattern of 5-HT(3A) and 5-HT(3B) subunits in human hippocampus appears to differ with the rodent counterpart, which may underlie the differences in some of the behavioural effects of 5-HT(3) receptor antagonists between these species.

The present study generated a polyclonal antibody (AP86/3) that recognises a peptide sequence of the h5-HT(3B) receptor subunit. Western blot analysis of homogenates prepared from cell lines expressing either homomeric (h5-HT(3A)) or heteromeric (h5-HT(3A/3B)) receptors, as well as immunocytochemical studies with the same cell lines, indicated that AP86/3 recognised, selectively, the 5-HT(3B) subunit. Immunohistochemical labelling was also apparent in cells in the rat hippocampus that displayed the distribution and morphology of interneurones.

The present study determined the detailed pharmacological profile of heterologously expressed human (h) homomeric 5-HT3A receptors in direct comparison to heteromeric h5-HT3A/3B receptors. The very minor differences in their respective pharmacological profiles indicates that the 5-HT3B receptor subunit alters, predominantly, the biophysical rather than the pharmacological properties of the 5-HT3 receptor.