Abstract
BackgroundThree dopamine receptor genes have been identified that are highly conserved among arthropod species. One of these genes, referred to in honey bees as Amdop2, shows a close phylogenetic relationship to the a-adrenergic-like octopamine receptor family. In this study we examined in parallel the functional and pharmacological properties of AmDOP2 and the honey bee octopamine receptor, AmOA1. For comparison, pharmacological properties of the honey bee dopamine receptors AmDOP1 and AmDOP3, and the tyramine receptor AmTYR1, were also examined.Methodology/Principal FindingsUsing HEK293 cells heterologously expressing honey bee biogenic amine receptors, we found that activation of AmDOP2 receptors, like AmOA1 receptors, initiates a rapid increase in intracellular calcium levels. We found no evidence of calcium signaling via AmDOP1, AmDOP3 or AmTYR1 receptors. AmDOP2- and AmOA1-mediated increases in intracellular calcium were inhibited by 10 µM edelfosine indicating a requirement for phospholipase C-β activity in this signaling pathway. Edelfosine treatment had no effect on AmDOP2- or AmOA1-mediated increases in intracellular cAMP. The synthetic compounds mianserin and epinastine, like cis-(Z)-flupentixol and spiperone, were found to have significant antagonist activity on AmDOP2 receptors. All 4 compounds were effective antagonists also on AmOA1 receptors. Analysis of putative ligand binding sites offers a possible explanation for why epinastine acts as an antagonist at AmDOP2 receptors, but fails to block responses mediated via AmDOP1.Conclusions/SignificanceOur results indicate that AmDOP2, like AmOA1, is coupled not only to cAMP, but also to calcium-signalling and moreover, that the two signalling pathways are independent upstream of phospholipase C-β activity. The striking similarity between the pharmacological properties of these 2 receptors suggests an underlying conservation of structural properties related to receptor function. Taken together, these results strongly support phylogenetic analyses indicating that the AmDOP2 and AmOA1 receptor genes are immediate paralogs.
Highlights
Some invertebrate and vertebrate dopamine (DA) receptor types demonstrate a strong phylogenetic relationship that is reflected in an apparent conservation of common functional properties [1,2,3]
AmDOP2 receptors couple to Ca2+ signaling pathways We found that exposure of AmDOP2-expressing HEK293 cells to
AmDOP2 receptors and AmOA1 receptors couple to cAMP signaling via a PLCb-independent pathway To determine if AmDOP2 and AmOA1 receptors are coupled to intracellular Ca2+ signaling via a PLCb-mediated pathway we investigated the effect of the PLC inhibitor, edelfosine [25]
Summary
Some invertebrate and vertebrate dopamine (DA) receptor types demonstrate a strong phylogenetic relationship that is reflected in an apparent conservation of common functional properties [1,2,3]. Phylogenetic analyses indicate that at least one DA receptor type may be specific to invertebrate species [1,7] The presence of this ‘invertebrate-type’ DA receptor (Figure 1) raises a number of interesting questions about the origin, function and role of this receptor protein in the invertebrate nervous system. Stimulation of cells expressing the DAMB/Dop99B receptor with DA induces a rapid, transient increase in intracellular calcium (Ca2+) levels [9,14,15] This property has yet to be demonstrated in other invertebrate-type DA receptors. Three dopamine receptor genes have been identified that are highly conserved among arthropod species One of these genes, referred to in honey bees as Amdop, shows a close phylogenetic relationship to the a-adrenergic-like octopamine receptor family. Pharmacological properties of the honey bee dopamine receptors AmDOP1 and AmDOP3, and the tyramine receptor AmTYR1, were examined
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