Differential composition of 5-hydroxytryptamine3 receptors synthesized in the rat CNS and peripheral nervous system.
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-HT3A) and subunit B (5-HT3B). We used in situ hybridization histochemistry and reverse transcriptase-PCR amplification to demonstrate that 5-HT3A subunit transcripts are expressed in central and peripheral neurons. In contrast, 5-HT3B subunit transcripts are restricted to peripheral neurons. Thus, the prevalent form of 5-HT3 receptor synthesized within the CNS lacks the 5-HT3B subunit. Because coexpression of 5-HT3A and 5-HT3B subunits produces heteromeric 5-HT3A/3B receptors with properties that differ from those of 5-HT3A homomeric receptors, we investigated possible coexpression of both subunits at the cellular level. We found that near to 90% of all 5-HT3B expressing neurons coexpress the 5-HT3A subunit in superior cervical and nodose ganglia (NG). In addition, there is a cellular population that expresses only the 5-HT3A subunit. Therefore, peripheral neurons have the capacity to synthesize two different 5-HT3 receptors, 5-HT3A+/3B- and 5-HT3A+/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-HT3A or 5-HT3A/3B subunits. Thus, presynaptic 5-HT3 receptors containing the 5-HT3B 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.
Morales
Marisela
M
National Institute on Drug Abuse, Cellular Neurophysiology, Baltimore, Maryland 21224, USA. mmorales@intra.nida.nih.gov
Wang
Shwun-De
SD
D000818:Animals; D001345:Autoradiography; D002451:Cell Compartmentation; D002452:Cell Count; D048429:Cell Size; D002490:Central Nervous System / Q000737:chemistry / Q000378:metabolism*; D005456:Fluorescent Dyes; D017403:In Situ Hybridization; D008297:Male; D009197:Myenteric Plexus / Q000737:chemistry / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009620:Nodose Ganglion / Q000737:chemistry / Q000378:metabolism; D017933:Peripheral Nervous System / Q000737:chemistry / Q000378:metabolism*; D021122:Protein Subunits; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D044406:Receptors, Serotonin, 5-HT3; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013266:Stilbamidines; D017783:Superior Cervical Ganglion / Q000737:chemistry / Q000378:metabolism
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D005456:Fluorescent Dyes; D021122:Protein Subunits; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D013266:Stilbamidines