Identification of 5-HT3A and 5-HT3B receptor subunits in human hippocampus.
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.
Brady
Catherine A
CA
Cellular and Molecular Neuropharmacology Research Group, Department of Pharmacology, Division of Neuroscience, The Medical School, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Dover
Terri J
TJ
Massoura
Andrew N
AN
Princivalle
Alesandra P
AP
Hope
Anthony G
AG
Barnes
Nicholas M
NM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007536:Isomerism; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D044406:Receptors, Serotonin, 5-HT3