Pharmacological characterization of a tyramine receptor from the southern cattle tick, Rhipicephalus (Boophilus) microplus

Authors: GROSS, AARON - Iowa State University; Temeyer, Kevin; DAY, TIME - Iowa State University; Perez De Leon, Adalberto - Beto; KIMBER, MICHAEL - Iowa State University; COATS, JOEL - Iowa State University

Submitted to: Insect Biochemistry and Molecular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/27/2015
Publication Date: 5/6/2015
Publication URL: http://handle.nal.usda.gov/10113/61880
Citation: Gross, A.D., Temeyer, K.B., Day, T.A., Perez De Leon, A.A., Kimber, M.J., Coats, J.R. 2015. Pharmacological characterization of a tyramine receptor from the southern cattle tick, Rhipicephalus (Boophilus) microplus. Insect Biochemistry and Molecular Biology. 63:47-53.

Interpretive Summary: The southern cattle fever tick is a parasite of cattle capable of transmitting at least two potentially fatal diseases to cattle. Resistance to chemical acaricides has become a major obstacle for control of this wide spread tick and the diseases it transmits. Amitraz is an acaricide that has been frequently used for control of the cattle tick, but increasing development of amitraz resistance has reduced its capability for tick control. Amitraz is believed to target the octopamine receptor in ticks interfering with normal tick metabolism and development. Studies to express and biochemically characterize the presumptive octopamine receptor of the tick using molecular biological techniques were initiated to clarify the identity of the presumptive octopamine receptor and its role in tick metabolism and resistance to amitraz. Recombinant tick octopamine receptor was expressed in cultured cells and biochemically characterized. Results of these studies demonstrated that the presumptive octopamine receptor was actually a tyramine receptor rather than an octopamine receptor and identified several biochemical compounds that could functionally activate or inhibit the receptor response to tyramine. In addition to clarifying the identity of the tick receptor protein, this study identified chemicals that may be used to test the role of the receptor in ticks that are either sensitive or resistant to amitraz, potentially providing information allowing better management of tick resistance and/or development of new chemicals for tick control.

Technical Abstract: The southern cattle fever tick (Rhipicephalus microplus) is a hematophagous external parasite that vectors the causative agents (Babesia spp.), which results in cattle fever or red water fever. The southern cattle fever tick is a threat to the cattle industry in many locations throughout the world. Control methods include the use of chemical acaricides including amitraz, a formamidine insecticide, which is proposed to activate octopamine receptors. Previous studies have identified a putative octopamine receptor from the southern cattle fever tick in Australia and the Americas. Furthermore, this putative octopamine receptor could play a role in acaricide resistance to amitraz. Recently, sequence data indicated that this putative octopamine receptor is actually a type-1 tyramine receptor (TAR1). In this study, the putative TAR1 was heterologously expressed in Chinese hamster ovary (CHO-K1) cells, and the expressed receptor resulted in a 39-fold higher affinity for tyramine compared to octopamine. Furthermore, the expressed receptor was strongly antagonized by yohimbine and cyproheptadine, and mildly antagonized by mianserin and phentolamine. Tolazoline and naphazoline had strong agonistic or modulatory activity against the expressed receptor, as did the amitraz metabolite, BTS-27271; however, this was only observed in the presence of tyramine. The southern cattle fever tick's tyramine receptor may serve as a target for the development of anti-parasitic compounds, in addition to being a potential target of formamidine insecticides.