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

ABSTRACT: 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-HT(2beta) and 5-HT(1alpha). In so doing, we also report the first functional expression of a crustacean 5-HT(1) receptor, and show that it inhibits accumulation of cAMP. The drugs mCPP and quipazine are 5-HT(1alpha) agonists and are ineffective at 5-HT(2beta). Conversely, methiothepin and cinanserin are antagonists of 5-HT(2beta) but do not block 5-HT(1alpha). 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.

SUBMITTER: Spitzer N

PROVIDER: S-EPMC4019008 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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

Spitzer Nadja N Edwards Donald H DH Baro Deborah J DJ

The Journal of experimental biology 20080101 Pt 1

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-HT(2b ...[more]

PMID: 18083737

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Project description:BackgroundSerotonin (5-HT) is a potent regulator of adult neurogenesis in the crustacean brain, as in the vertebrate brain. However, there are relatively few data regarding the mechanisms of serotonin's action and which precursor cells are targeted. Therefore, we exploited the spatial separation of the neuronal precursor lineage that generates adult-born neurons in the crayfish (Procambarus clarkii) brain to determine which generation(s) is influenced by serotonin, and to identify and localize serotonin receptor subtypes underlying these effects.ResultsRT-PCR shows that mRNAs of serotonin receptors homologous to mammalian subtypes 1A and 2B are expressed in P. clarkii brain (referred to here as 5-HT1α and 5-HT2β). In situ hybridization with antisense riboprobes reveals strong expression of these mRNAs in several brain regions, including cell clusters 9 and 10 where adult-born neurons reside. Antibodies generated against the crustacean forms of these receptors do not bind to the primary neuronal precursors (stem cells) in the neurogenic niche or their daughters as they migrate, but do label these second-generation precursors as they approach the proliferation zones of cell clusters 9 and 10. Like serotonin, administration of the P. clarkii 5-HT1α-specific agonist quipazine maleate salt (QMS) increases the number of bromodeoxyuridine (BrdU)-labeled cells in cluster 10; the P. clarkii 5-HT2β-specific antagonist methiothepin mesylate salt (MMS) suppresses neurogenesis in this region. However, serotonin, QMS and MMS do not alter the rate of BrdU incorporation into niche precursors or their migratory daughters.ConclusionOur results demonstrate that the influences of serotonin on adult neurogenesis in the crayfish brain are confined to the late second-generation precursors and their descendants. Further, the distribution of 5-HT1α and 5-HT2β mRNAs and proteins indicate that these serotonergic effects are exerted directly on specific generations of neuronal precursors. Taken together, these results suggest that the influence of serotonin on adult neurogenesis in the crustacean brain is lineage dependent, and that 5-HT1α and 5-HT2β receptors underlie these effects.

Dataset Information

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

Publications

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

Similar Datasets

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