Larvae of the small white butterfly, Pieris rapae, express a novel serotonin receptor
The biogenic amine serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter in vertebrates and invertebrates. It acts in regulation and modulation of many physiological and behavioral processes through G protein-coupled receptors. Insects express five 5-HT receptor subtypes that share high similarity with mammalian 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B and 5-HT7 receptors. We isolated a cDNA (Pr5-HT8) from larval Pieris rapae, which shares relatively low similarity to the known 5-HT receptor classes. After heterologous expression in HEK-293 cells, Pr5-HT8 mediated increased [Ca2+]i in response to low concentrations (<10 nM) of 5-HT. The receptor did not affect [cAMP]i even at high concentrations (>10 μM) of 5-HT. Dopamine, octopamine and tyramine did not influence receptor signaling. Pr5-HT8 was also activated by various 5-HT receptor agonists including 5-methoxytryptamin, (±)-8-Hydroxy-2-(dipropylamino) tetralin and 5-carboxamidotryptamine. Methiothepin, a nonselective 5-HT receptor antagonist, activated Pr5-HT8. WAY 10635, a 5-HT1A antagonist, but not SB-269970, SB-216641 or RS- 127445, inhibited 5-HT-induced [Ca2+]i increases. We infer that Pr5-HT8 represents the first recognized member of a novel 5-HT receptor class with a unique pharmacological profile. We found orthologs of Pr5-HT8 in some insect pests and vectors such as beetles and mosquitoes, but not in the genomes of honeybee or parasitoid wasps. This is likely to be an invertebrate-specific receptor because there were no similar receptors in mammals.
Keywords: 5-hydroxytryptamine, serotonin, neurotransmitter, GPCR, pharmacology, insecticide
