Pharmacological Characterization of a 5-HT₁-Type Serotonin Receptor in the Red Flour Beetle, <i>Tribolium castaneum</i>

<div><p>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, <i>Tribolium castaneum</i> (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 Ca²⁺ 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 <i>T. castaneum</i> 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.</p>