Differential Composition of 5-Hydroxytryptamine3Receptors Synthesized in the Rat CNS and Peripheral Nervous System

Abstract

The type 3 serotonin (5-HT₃) receptor is the only ligand-gated ion channel receptor for serotonin in vertebrates. Two 5-HT₃ receptor subunits have been cloned, subunit A (5-HT_3A) and subunit B (5-HT_3B). We used <i>in situ</i> hybridization histochemistry and reverse transcriptase-PCR amplification to demonstrate that 5-HT_3Asubunit transcripts are expressed in central and peripheral neurons. In contrast, 5-HT_3B subunit transcripts are restricted to peripheral neurons. Thus, the prevalent form of 5-HT₃receptor synthesized within the CNS lacks the 5-HT_3Bsubunit. Because coexpression of 5-HT_3A and 5-HT_3B subunits produces heteromeric 5-HT_3A/3Breceptors with properties that differ from those of 5-HT_3Ahomomeric receptors, we investigated possible coexpression of both subunits at the cellular level. We found that near to 90% of all 5-HT_3B expressing neurons coexpress the 5-HT_3Asubunit in superior cervical and nodose ganglia (NG). In addition, there is a cellular population that expresses only the 5-HT_3A subunit. Therefore, peripheral neurons have the capacity to synthesize two different 5-HT₃ receptors, 5-HT_3A+/_3B− and 5-HT_3A+/_3B+ 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_3A or 5-HT_3A/3B subunits. Thus, presynaptic 5-HT₃ receptors containing the 5-HT_3B subunit might be present in these target brain areas. The compartmentalized structural composition of the 5-HT₃ receptor may be the basis of functional diversity within this receptor. This raises the possibility that 5-HT₃ receptors participating in sympathetic, parasympathetic and sensory functions may be functionally different from those involved in cognition and emotional behavior.