Functional characterization of a novel serotonin receptor (5-HTap2) expressed in the CNS of Aplysia californica.
Serotonin has been shown to be a neuromodulator in the Aplysia californica CNS. The diversity of serotonin actions is due to the existence of several different receptor subtypes. In this study we report the cloning of a full-length cDNA, coding for a novel serotonin receptor (5-HTap2). The receptor protein bears the characteristics of G protein-coupled receptors. It shares 68% and 34% of its amino acid sequence identity with the 5-HTlym receptor from Lymnaea stagnalis and the mammalian 5-HT1A receptor, respectively. When transfected in HEK 293 cells, 5-HTap2 was negatively coupled to adenylate cyclase. Ligand binding analysis indicated that the order of potencies of various drugs for the inhibition of [3H]LSD binding was: methiothepin > metergoline > 5-CT > PAPP > 5-HT > ketanserin > NAN-190 > 8-OH-DPAT > clozapine. RT-PCR amplification of RNA isolated from different tissues indicated that this receptor is expressed in the CNS and in bag cells. The expression of 5-HTap2 restricted to the CNS suggests an important role for this receptor in the modulation of neuronal functions in Aplysia. Moreover, the high expression of 5-HTap2 in the bag cells, associated with its pharmacological profile, suggests that this receptor may be implicated in modulating the afterdischarge during the egg-laying behavior.
Barbas
Demian
D
Department de biochimie, Université de Montreal, Québec, Canada.
Zappulla
Jacques P
JP
Angers
Stéphane
S
Bouvier
Michel
M
Castellucci
Vincent F
VF
DesGroseillers
Luc
L
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia; D019556:COS Cells; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000493:pharmacokinetics; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology; D014316:Tritium
D000067956:Adenylyl Cyclase Inhibitors; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D014316:Tritium; D012701:Serotonin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases