Evidence for expression of heteromeric serotonin 5-HT(3) receptors in rodents.
The gene and cDNAs that encode a novel subunit of rodent serotonin 5-HT(3) receptors were isolated from mouse and rat tissues. Each of the new rodent subunits shares 40% amino acid identity with the rat 5-HT(3A) subunit and 73% identity with the human 5-HT(3B) subunit. Despite a relatively low level of structural conservation, sequence analysis and functional studies suggest that the new rodent subunits are orthologues of the human 5-HT(3B) subunit. In common with homologous human receptors, rat heteromeric 5-HT(3) receptors displayed a substantially larger single-channel conductance than homomeric 5-HT(3A) receptors. In addition, the rat heteromeric receptors were less sensitive to antagonism by tubocurarine. However, in contrast to human heteromeric receptors, those of the rat displayed pronounced inward rectification of both the whole-cell and single-channel current amplitudes. Transcripts of the mouse 5-HT(3A) and 5-HT(3B) subunits are coexpressed in several cell lines that possess endogenous 5-HT(3) receptors. In addition, treatment of rat PC12 cells with nerve growth factor induced expression of both subunit mRNAs, with a similar time course for accumulation of each transcript. The combination of functional data and expression patterns is consistent with the existence of heteromeric 5-HT(3) receptors in rodent neurons.
Hanna
M C
MC
The Institute for Genomic Research, Rockville, Maryland Department of Pharmacology, The George Washington University Medical Center, Washington, D.C., USA.
Davies
P A
PA
Hales
T G
TG
Kirkness
E F
EF
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004553:Electric Conductivity; D015870:Gene Expression; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D016716:PC12 Cells; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011985:Receptors, Serotonin / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D044406:Receptors, Serotonin, 5-HT3; D011994:Recombinant Proteins / Q000378:metabolism; D017385:Sequence Homology
D018076:DNA, Complementary; D046911:Macromolecular Substances; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D011994:Recombinant Proteins