Insect ryanodine receptors: molecular targets for novel pest control chemicals

Abstract

Ryanodine receptors (RyRs) are a distinct class of ligand-gated calcium channels controlling the release of calcium from intracellular stores. They are located on the sarcoplasmic reticulum of muscle and the endoplasmic reticulum of neurons and many other cell types. Ryanodine, a plant alkaloid and an important ligand used to characterize and purify the receptor, has served as a natural botanical insecticide, but attempts to generate synthetic commercial analogues of ryanodine have proved unsuccessful. Recently two classes of synthetic chemicals have emerged resulting in commercial insecticides that target insect RyRs. The phthalic acid diamide class has yielded flubendiamide, the first synthetic ryanodine receptor insecticide to be commercialized. Shortly after the discovery of the phthalic diamides, the anthranilic diamides were discovered. This class has produced the insecticides Rynaxypyr and Cyazypyr. Here we review the structure and functions of insect RyRs and address the modes of action of phthalic acid diamides and anthranilic diamides on insect ryanodine receptors. Particularly intersting is the inherent selectivity both chemical classes exhibit for insect RyRs over their mammalian counterparts. The future prospects for RyRs as a commercially-validated target site for insect control chemicals are also considered.

Identification of ion channel genes in the Acyrthosiphon pisum genome

“…They are located in the sarcoplasmic reticulum of skeletal muscle, where calcium release is important in muscle contraction, and also in the endoplasmic reticulum of neurons and other cell types, where they are heavily involved in calcium signalling (Sattelle et al, 2008). Each receptor is composed of a large cytoplasmic domain at the N terminus and a small transmembrane domain at the C terminus (Hamilton, 2005).…”

“…Compared with the D. melanogaster gene which is composed of twenty-six exons, with exons 9a/b being mutually exclusive and exon 13 having an optional splice site, the A. pisum receptor has an estimated 98 exons and no equivalent splice sites. The recently commercialized synthetic insecticide Cyazypyr™, which targets the ryanodine receptors of aphids, acts as a channel activator and binds at a site distinct from the ryanodine binding site (Sattelle et al, 2008).…”

“…Recently, a new class of insecticides was launched, targeting ryanodine receptors of lepidopteran and sucking pests. This class includes Cyazypyr™ and Rynaxypyr® (Sattelle et al, 2008) and these compounds will enable aphid control in previously resistant populations.…”

Insecticidal Activity of Dienamides on Cabbage Caterpillar and Beneficial Insects

“…The average body weights of the insects were 1.40 mg for the A. monuste second instar larvae, Figure 1. Syntheses of the amides (1)(2)(3)(4)(5)(6)(7)(8)(9) from potassium sorbate. Amines employed in the syntheses, reaction yields and melting points of the amides are described in Table 1 Table 1.…”

“…As an example of these natural molecules we have pyrethrum, nicotine, ryanodine and amides, extracted from Chrysanthemum cinerariifolium, Nicotiana sp., Ryania speciosa, and Piper nigrum, respectively. [5][6][7][8] Among the major groups of agricultural pests are the butterflies, which include Ascia monuste (Godart 1819) (Lepidoptera: Pieridae). This pest is present in South America, Central America and North America and attacks plants of the Brassicaceae family such as cabbage, broccoli, cauliflower, tall cabbage, brussels sprout, kohlrabi, Chinese cabbage, mustard, canola, cress, radish and arugula.…”