Octopamine and tyramine signaling in <i>Aedes aegypti:</i> characterization, distribution and potential role in the Dengue vector development and physiology

Abstract In insects, the biogenic amines octopamine (OA) and tyramine (TA) are involved in controlling several physiological and behavioural processes. OA and TA act as neurotransmitters, neuromodulators or neurohormones, performing their functions by binding to specific receptors belonging to the G protein-coupled receptor (GPCR) superfamily. OA and TA along with their receptors are involved in reproduction, smell perception, metabolism, and homeostasis. Moreover, OA and TA receptors are targets for insecticides and antiparasitic agents, such as the formamidine Amitraz. In the dengue and yellow fever vector, Aedes aegypti , limited research has been previously reported on their OA or TA receptors. Here, we identify and characterize the OA and TA receptors in A. aegypti . Bioinformatic tools have been used to identify four OA and three TA receptors in the genome of A. aegypti . The seven receptors are expressed in all developmental stages of A. aegypti ; however, their highest transcript abundance is observed in the adult compared to the larval stages. Among several adult A. aegypti tissues examined, including the central nervous system, antennae and rostrum, midgut, Malpighian tubules, ovaries, and testes, the type 2 TA receptor (TAR2) transcript is most abundant in the ovaries and the type 3 TA receptor (TAR3) is enriched in the Malpighian tubules, leading us to hypothesize putative roles for these receptors in reproduction and diuresis, respectively. Furthermore, a blood meal influenced OA and TA receptor transcript expression patterns in adult female tissues at several time points post blood meal, suggesting these receptors may play key physiological roles associated with feeding. To better understand OA and TA signaling in A. aegypti , the transcript expression profiles of key enzymes in their biosynthetic pathway, namely tyrosine decarboxylase ( Tdc ) and tyramine β-hydroxylase ( T β h ), were examined in developmental stages, adult tissues, and brains from blood-fed females. These findings provide information for better understanding the physiological roles of OA, TA, and their receptors in A. aegypti , and additionally, may help in the development of novel strategies for the control of these human disease vectors. Author summary Aedes aegypti is the primary vector for dengue, chikungunya, and yellow fever – debilitating diseases that together are responsible for hundreds of millions of infections and thousands of deaths annually worldwide. Understanding the A. aegypti physiology may be critical for the development of new control strategies. In insects, the biogenic amines dopamine, serotonin, tyramine and octopamine play important roles in controlling various physiological processes. In A. aegypti , both serotonin and dopamine are implicated in blood feeding behavior and development. Conversely, the role of octopamine (OA) and tyramine (TA) in A. aegypti physiology is still poorly characterized. Both OA and TA exert their physiological actions by interacting with and activating different receptors, the tyramine (TAR) and the octopamine (OAR) receptors. Here, we show the characterization of the OA and TA receptors in A. aegypti . In the A. aegypti genome we identify a total of four OA receptors and three TA receptors, suggesting for each receptor a particular role in the development and physiology of this insect. This work contributes to better understanding the roles of OA, TA, and their receptors, in A. aegypti development and physiology. Furthermore, it may be crucial in identifying novel strategies for the mosquitoes control.

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