Invertebrate specific D1‐like dopamine receptor in control of salivary glands in the black‐legged tick Ixodes scapularis

Abstract

The control of tick salivary secretion, which plays a crucial role in compromising the host immune system, involves complex neural mechanisms. Dopamine is known to be the most potent activator of salivary secretion, as a paracrine/autocrine factor. We describe the invertebrate specific D1-like dopamine receptor (InvD1L), which is highly expressed in tick salivary glands. The InvD1L phylogenic clade was found only in invertebrates, suggesting that this receptor was lost in the vertebrates during evolution. InvD1L expressed in CHO-K1 cells was activated by dopamine with a median effective dose (EC50) of 1.34 μM. Immunohistochemistry using the antibody raised against InvD1L revealed two different types of immunoreactivities: basally located axon terminals that are colocalized with myoinhibitory peptide (MIP) and SIFamide neuropeptides, and longer axon-like processes that are positive only for the InvD1L antibody and extended to the apical parts of the acini. Both structures were closely associated with the myoepithelial cell, as visualized by beta-tubulin antibody, lining the acinar lumen in a web-like fashion. Subcellular localizations of InvD1L in the salivary gland suggest that InvD1L modulates the neuronal activities including MIP/SIFamide varicosities, and leads the contraction of myoepithelial cells and/or of the acinar valve to control the efflux of the luminal content. Combining the previously described D1 receptor with its putative function for activating an influx of fluid through the epithelial cells of acini, we propose that complex control of the tick salivary glands is mediated through two different dopamine receptors, D1 and InvD1L, for different downstream responses of the acinar cells.

Autocrine/paracrine dopamine in the salivary glands of the blacklegged tick Ixodes scapularis

“…4A) coincide with the rapid engorgement of blood in our feeding model, during which up to 75% of water from imbibed and digested blood meal is excreted back to a host via SG (Sauer and Hair, 1971; Kaufman and Phillips, 1973). Nevertheless, the role of the SG as the autocrine/paracrine target of DA that triggers tick salivary secretion was also described in our previous studies (Simo et al, 2011; Simo et al, 2013b). …”

“…The D1 receptor, located on the luminal surface of epithelial cell types, was proposed to function as an activator of inward fluid transport (Simo et al, 2011). The InvD1L receptor, expressed in neuropeptidergic axon terminals and in other luminal axon-like processes (Simo et al, 2013b), was thought to control myoepithelial cells and/or the acinar valve to export the luminal saliva out through the SG ducts. It is also worth noting that the data quantifying DA levels throughout the duration of feeding measured by HPLC-ECD is not congruent with the times of DA-immunoreactive granules in the basal acini, which appeared only 24 to 48 hours after the onset of the feeding (Simo et al, 2011).…”

“…Although there is no specific adrenergic receptor described in arthropods, NE has significant levels of cross-activity on DA receptors and on the D1 receptor of I. scapularis in particular (Simo et al, 2013b). The level of NE in salivary secretions was less than quantifiable (lower than ∼100fg).…”

Orchestration of salivary secretion mediated by two different dopamine receptors in the blacklegged tickIxodes scapularis

“…Expression plasmids were prepared for high purity and concentrations (>1 μg μl −1 ) and were then sequenced. Functional G-protein-coupled receptor expression was performed based on a previous description with modifications (Park et al, 2003;Šimo et al, 2011;Jiang et al, 2013;Šimo et al, 2014). A one-to-one mixture of the receptor-containing plasmid and the codon-optimised human apoaequorin-containing plasmid (Vernon and Printen, 2002) ; AAT Bioquest, Sunnyvale, CA, USA) was added to the resuspended cells.…”

Evaluation ofAaDOP2 Receptor Antagonists Reveals Antidepressants and Antipsychotics as Novel Lead Molecules for Control of the Yellow Fever Mosquito,Aedes aegypti

“…For example, the biogenic amine dopamine and its receptors are implicated in a variety of arthropod behaviors, including arousal (Kume et al, 2005), locomotion (Yellman et al, 1997;Draper et al, 2007;Mustard et al, 2010), and olfactory learning (Kim et al, 2007;Riemensperger et al, 2011). It is also notable that dopamine is associated with the salivary function of vectors (Ali, 1997;Sauer et al, 2000;Simo et al, 2011Simo et al, , 2014, suggesting potential roles for the mediation of pathogen acquisition and transmission during blood feeding. In Aedes aegypti, dopamine is also implicated in sclerotization and ovarian/egg development, as increased dopamine levels were observed in newly emerged s This article has supplemental material available at jpet.aspetjournals.org.…”