Functional and pharmacological characterization of a tyramine receptor from the southern cattle tick, Rhipicephalus microplus

The southern cattle tick, Rhipicephalus (Boophilus) microplus, vectors the causative agents (Babesia spp.) that result in Texas Cattle Fever.  The tick is a continuing threat to the United States, which currently maintains a permanent quarantine zone along the Texas-Mexico border.  Detection of the southern cattle tick, inside or outside of this quarantine area, results in either chemical acaricide treatment or pasture vacation for several months.  Recently, several tick populations resistant to various chemical acaricides have been detected in Mexico.  This includes ticks that are resistant to amitraz, a formamidine insecticide, which is believed to work at octopamine receptors.  Previously, a putative octopamine receptor was reported from susceptible and resistant populations of R. microplus.  A two-site mutation has been observed in a G-protein-coupled receptor (GPCR), which preferentially responds to tyramine.  However, characterization of this target as a potential resistance mechanism has not been investigated.  Here we functionally and pharmacologically characterized this receptor.  In addition, we characterized its interaction with formamidine parent compounds and metabolites.