Abstract

The type 3 serotonin (5-HT<sub>3</sub>) receptor is the only ligand-gated ion channel receptor for serotonin in vertebrates. Two 5-HT<sub>3</sub> receptor subunits have been cloned, subunit A (5-HT<sub>3A</sub>) and subunit B (5-HT<sub>3B</sub>). We used <i>in situ</i> hybridization histochemistry and reverse transcriptase-PCR amplification to demonstrate that 5-HT<sub>3A</sub>subunit transcripts are expressed in central and peripheral neurons. In contrast, 5-HT<sub>3B</sub> subunit transcripts are restricted to peripheral neurons. Thus, the prevalent form of 5-HT<sub>3</sub>receptor synthesized within the CNS lacks the 5-HT<sub>3B</sub>subunit. Because coexpression of 5-HT<sub>3A</sub> and 5-HT<sub>3B</sub> subunits produces heteromeric 5-HT<sub>3A/3B</sub>receptors with properties that differ from those of 5-HT<sub>3A</sub>homomeric receptors, we investigated possible coexpression of both subunits at the cellular level. We found that near to 90% of all 5-HT<sub>3B</sub> expressing neurons coexpress the 5-HT<sub>3A</sub>subunit in superior cervical and nodose ganglia (NG). In addition, there is a cellular population that expresses only the 5-HT<sub>3A</sub> subunit. Therefore, peripheral neurons have the capacity to synthesize two different 5-HT<sub>3</sub> receptors, 5-HT<sub>3A</sub>+/<sub>3B</sub>− and 5-HT<sub>3A</sub>+/<sub>3B</sub>+ receptors. We also determined that neurons of NG projecting to the nucleus tractus solitarium and those of dorsal root ganglia projecting to superficial layers of the spinal cord express 5-HT<sub>3A</sub> or 5-HT<sub>3A/3B</sub> subunits. Thus, presynaptic 5-HT<sub>3</sub> receptors containing the 5-HT<sub>3B</sub> subunit might be present in these target brain areas. The compartmentalized structural composition of the 5-HT<sub>3</sub> receptor may be the basis of functional diversity within this receptor. This raises the possibility that 5-HT<sub>3</sub> receptors participating in sympathetic, parasympathetic and sensory functions may be functionally different from those involved in cognition and emotional behavior.

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