Conservation of structure, signaling and pharmacology between two serotonin receptor subtypes from decapod crustaceans, Panulirus interruptus and Procambarus clarkii

Serotonin (5-HT) plays important roles in the maintenance and modulation of neural systems throughout the animal kingdom. The actions of 5-HT have been well characterized for several crustacean model circuits; however, a dissection of the serotonergic transduction cascades operating in these models has been hampered by the lack of pharmacological tools for invertebrate receptors. Here we provide pharmacological profiles for two 5-HT receptors from the swamp crayfish, Procambarus clarkii: 5-HT2 beta and 5-HT1 alpha. In so doing, we also report the first functional expression of a crustacean 5-HT1 receptor, and show that it inhibits accumulation of cAMP. The drugs mCPP and quipazine are 5-HT1 alpha agonists and are ineffective at 5-HT2 beta. Conversely, methiothepin and cinanserin are antagonists of 5-HT2 beta but do not block 5-HT1 alpha. A comparison of these two receptors with their orthologs from the California spiny lobster, Panulirus interruptus, indicates conservation of protein structure, signaling and pharmacology. This conservation extends beyond crustacean infraorders. The signature residues that form the ligand-binding pocket in mammalian 5-HT receptors are found in the crustacean receptors. Similarly, the protein domains involved in G protein coupling are conserved between the two crustacean receptors and other characterized arthropod and mammalian 5-HT receptors. Considering the apparent conservation of pharmacological properties between crustacean 5-HT receptors, these tools could be applicable to related crustacean physiological preparations.