Phenyl imidazolidin‐2‐ones antagonize a β‐adrenergic‐like octopamine receptor in diamondback moth (Plutella xylostella)

Abstract

BACKGROUND: The diamondback moth (Plutella xylostella) is one of the most destructive lepidopteran pests on cruciferous vegetables. However, resistance has emerged to current chemical and biological insecticides used for P. xylostella control, indicating the necessity of screening new targets on P. xylostella, and finding new insecticides against P. xylostella. In particular, octopamine receptors are representative G protein-coupled receptors found only in invertebrates and are potential targets for identifying novel insecticides.RESULTS: A ⊎-adrenergic-like octopamine receptor gene (PxOA2B1) was cloned, and its pharmacological characteristics in P. xylostella were studied. The results demonstrated that octopamine could activate the PxOA2B1 receptor, with a half-maximal effective concentration (EC 50 ) of 49.5 nM. Amitraz, an insecticide and acaricide, and its metabolite (N-2,4-dimethylphenyl-N 0methylformamidine; DPMF) were also found to act as PxOAB1R agonists. We synthesized phenyl imidazolidin-2-one derivatives 3a-h using DPMF as the lead compound, and compounds 3a-h showed similar antagonist activities as phentolamine, mianserin and chlorpromazine. In particular, 3d, with an EC 50 of 25.2 nM, showed very similar antagonist activity to mianserin.CONCLUSION: This research found that PxOAB1R might be a potential target for P. xylostella control. Phenyl imidazolidin-2-ones could be novel potential antagonists targeted at octopamine receptors and would be useful tools for the design and development of novel insecticides.

Pharmacological Properties and Function of the PxOctβ3 Octopamine Receptor in Plutella xylostella (L.)

“…In addition, the response of PxOctβ3 to dopamine was significant ( p ≤ 0.05), but the activation effect was much lower than that of octopamine. The effective medium concentration EC 50 of octopamine for PxOctβ3 was 6.50 × 10 −8 M, which was similar to that of Octβ1 [ 30 ] but lower than that of OA2B2 [ 28 ]. PxOctβ3 was more sensitive to octopamine than TcOctβ3 (EC 50 of 8.68 × 10 −7 M) but less sensitive than DmOctβ3 (EC 50 of 1.40 × 10 −8 M) [ 39 , 40 ].…”

“…Insect Octβ3Rs are specifically activated by either octopamine or tyramine, resulting in increased levels of intracellular cAMP [ 30 , 31 ]. Thus, corresponding experiments were conducted on transformed HEK293 cells that stably expressed PxOAB3.…”

“…However, TcOctβ3 has been found to be highly expressed in early larvae, and there may be differences in the level of expression of this gene among different species. In addition, we found that the level of expression of PxOctβ3 differed in females and males, which was also reflected in PxOctβ1 and PxOctβ2 [ 28 , 29 , 30 ]. In addition, this study confirmed that an increase in the nerve impulse responses of male pheromone-sensitive receptor neurons (RNs) after octopamine injection in silkworm ( Bombyx mori ) is either absent or less sensitive in females [ 44 ].…”

Molecular and pharmacological characterization of biogenic amine receptors from the diamondback moth, Plutella xylostella

“…Among the PxBARs, only two octopamine receptors, PxOA2B2 (XP_011568733) 59 and PxOA2B1 (XP_011557485.1), 60 and a type 1 tyramine receptor, PxTAR1 (QCC62350.1), 61 had been previously characterized. We physically cloned full‐length cDNAs and identified complete open reading frames.…”

PaOctβ2R: Identification and Functional Characterization of an Octopamine Receptor Activating Adenylyl Cyclase Activity in the American Cockroach Periplaneta americana

“…Coupling of PaOctβ2R to intracellular signaling cascades was examined via cell-endogenous G-proteins. PaOctβ2R, like other β-adrenergic-like octopamine receptors from insects [24][25][26]37,54,55] and mammalian β-adrenergic receptors (for a review, see: [56]), is positively coupled to adenylyl cyclase via Gs proteins, and causes an increase in [cAMP]i. With a mean EC50 of 4.67 × 10 −10 M, activation of PaOctβ2R was much more sensitive to octopamine than to tyramine (mean EC50 = 4.30 × 10 −8 M; Table 1).…”