5-HT3-receptor subunits A and B are co-expressed in neurons of the dorsal root ganglion

The type 3 serotonin (5-HT3) receptor is the only ligand-gated ion channel receptor for serotonin (5-HT), Many pharmacological, behavioral, and electrophysiological studies indicate heterogeneous properties for this receptor. Although the basis for this heterogeneity is unknown, one possible explanation for these findings resides in the subunit composition of the receptor, Two 5-HT3-receptor subunits have been cloned: the 5-HT3-receptor subunit A (5-HT3A) and the 5-HT3-receptor subunit B (5-HT3B). Recombinant co-expression of 5-HT3A and 5-HT3B subunits produces a functional heteromeric 5-HT3A/3B receptor with pharmacological and electrophysiological properties different from those displayed by the 5-HT3A homomeric receptor. In the present report, we used in situ hybridization histochemistry to demonstrate that the 5-HT3B subunit is expressed in rat dorsal root ganglion (DRG) neurons. We determined with cellular resolution that 5-HT3B subunit mRNA was expressed in 43.2 +/- 2.8% of the total population of DRG neurons. By comparison, the 5-HT3A subunit was more widely expressed, with 70.0 +/- 2.8% of the total population of DRG neurons expressing this subunit. Further analyses showed that most of the neurons containing mRNA for the 5-HT3B subunit (91.5 +/- 3.4%) also expressed the 5-HT3A subunit. In contrast, nearly half the population of neurons expressing 5-HT3A subunit lacked (52.8 +/- 5.9%) transcripts for the 5-HT3B subunit. These results provide the first evidence indicating that the 5-HT3B subunit of the 5-HT3 receptor is expressed in DRG and suggest that sensory neurons have the capacity to synthesize at least two structurally different 5-HT3 receptors: a heteromeric 5-HT3A/3B receptor and a homomeric 5-HT3A receptor. Consequently, 5-HT3 receptors with different properties might be present in peripheral and central axons of the DRG. These findings open the possibility that distinct types of 5-HT3 receptors may be involved in perception and/or processing of sensory information. J. Comp. Neurol. 438:163-172, 2001. Published 2001 Wiley-Liss, Inc.dagger.