title: Pharmacological characterization of a 5-HT1-type serotonin receptor in the red flour beetle, Tribolium castaneum.
abstract: Serotonin (5-hydroxytryptamine, 5-HT) is known for its key role in modulating diverse physiological processes and behaviors by binding various 5-HT receptors. However, a lack of pharmacological knowledge impedes studies on invertebrate 5-HT receptors. Moreover, pharmacological information is urgently needed in order to establish a reliable classification system for invertebrate 5-HT receptors. In this study we report on the molecular cloning and pharmacological characterization of a 5-HT1 receptor from the red flour beetle, Tribolium castaneum (Trica5-HT1). The Trica5-HT1 receptor encoding cDNA shows considerable sequence similarity with members of the 5-HT1 receptor class. Real time PCR showed high expression in the brain (without optic lobes) and the optic lobes, consistent with the role of 5-HT as neurotransmitter. Activation of Trica5-HT1 in mammalian cells decreased NKH-477-stimulated cyclic AMP levels in a dose-dependent manner, but did not influence intracellular Ca(2+) signaling. We studied the pharmacological profile of the 5-HT1 receptor and demonstrated that α-methylserotonin, 5-methoxytryptamine and 5-carboxamidotryptamine acted as agonists. Prazosin, methiothepin and methysergide were the most potent antagonists and showed competitive inhibition in presence of 5-HT. This study offers important information on a 5-HT1 receptor from T. castaneum facilitating functional research of 5-HT receptors in insects and other invertebrates. The pharmacological profiles may contribute to establish a reliable classification scheme for invertebrate 5-HT receptors.
authors.affiliation: Department of Animal Physiology and Neurobiology, Zoological Institute, KU Leuven, Leuven, Belgium.
authors.forename: Rut
authors.initials: R
authors.lastname: Vleugels
authors.forename: Cynthia
authors.initials: C
authors.lastname: Lenaerts
authors.forename: Arnd
authors.initials: A
authors.lastname: Baumann
authors.forename: Jozef
authors.initials: J
authors.lastname: Vanden Broeck
authors.forename: Heleen
authors.initials: H
authors.lastname: Verlinden
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D003001:Cloning, Molecular; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008969:Molecular Sequence Data; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic; D014231:Tribolium / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D000242:Cyclic AMP