Anthranilic diamides: A new class of insecticides with a novel mode of action, ryanodine receptor activation

Development of insecticides with unique modes of action is necessary to combat widespread insecticide resistance. A new class of insecticides has been discovered, the anthranilic diamides, that provides exceptional control through action on a novel target, the ryanodine receptor. Anthranilic diamides potently activate this receptor, releasing stored calcium from the sarcoendoplasmic reticulum causing impaired regulation of muscle contraction. Expression of a recombinant Drosophila ryanodine receptor in a lepidopteran cell line confers sensitivity to anthranilic diamides similar to that observed with native receptors. Ligand-binding studies with radiolabeled ryanodine and radiolabeled anthranilic diamide in Periplaneta americana reveal a single, saturable binding site for this chemistry distinct from that of ryanodine. Further, calcium mobilization studies using mammalian cell lines indicate anthranilic diamides exhibit >500-fold differential selectivity toward insect, over mammalian, receptors. Consequently, anthranilic diamides offer a novel pharmacological tool for calcium signaling research in addition to a unique alternative to existing pest-management strategies.

[1]  R. Tsien,et al.  A new generation of Ca2+ indicators with greatly improved fluorescence properties. , 1985, The Journal of biological chemistry.

[2]  R. Zucchi,et al.  The sarcoplasmic reticulum Ca2+ channel/ryanodine receptor: modulation by endogenous effectors, drugs and disease states. , 1997, Pharmacological reviews.

[3]  T. Narahashi.  Nerve membrane ion channels as the target site of insecticides. , 2002, Mini reviews in medicinal chemistry.

[4]  K. Mikoshiba,et al.  Requirement of the inositol trisphosphate receptor for activation of store-operated Ca2+ channels. , 2000, Science.

[5]  S. Marx,et al.  Coupled Gating Between Cardiac Calcium Release Channels (Ryanodine Receptors) , 2001, Circulation research.

[6]  K. D. Wing,et al.  Bioactivation and mode of action of the oxadiazine indoxacarb in insects , 2000 .

[7]  A. Marks,et al.  Stabilization of calcium release channel (ryanodine receptor) function by FK506-binding protein , 1994, Cell.

[8]  M. Poenie.  Alteration of intracellular Fura-2 fluorescence by viscosity: a simple correction. , 1990, Cell calcium.

[9]  S. Marx,et al.  Coupled gating between individual skeletal muscle Ca2+ release channels (ryanodine receptors) , 1998, Science.

[10]  J. Bloomquist.  Ion channels as targets for insecticides. , 1996, Annual review of entomology.

[11]  G. Lees,et al.  Dihydroavermectin B1: actions on cultured neurones from the insect central nervous system , 1986, Brain Research.

[12]  N. Tublitz,et al.  Insect cardioactive neuropeptides: peptidergic modulation of the intrinsic rhythm of an insect heart is mediated by inositol 1,4,5- trisphosphate , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  I. Pessah,et al.  Ryanodine stabilizes multiple conformational states of the skeletal muscle calcium release channel. , 1992, The Journal of biological chemistry.

[14]  G. Durst,et al.  Natural products as insecticides: the biology, biochemistry and quantitative structure-activity relationships of spinosyns and spinosoids. , 2001, Pest management science.

[15]  L. T. Wasserthal,et al.  Innervation of heart and alary muscles in Sphinx ligustri L. (Lepidoptera) , 1977, Cell and Tissue Research.

[16]  M. Berridge,et al.  Expression and Function of Ryanodine Receptors in Nonexcitable Cells (*) , 1996, The Journal of Biological Chemistry.

[17]  P. McCullagh,et al.  Generalized Linear Models , 1992 .

[18]  J. Putney,et al.  Capacitative calcium entry channels , 1999, BioEssays : news and reviews in molecular, cellular and developmental biology.

[19]  Ralf Nauen,et al.  New modes of action of insecticides , 2002 .

[20]  J. Truman,et al.  Insect cardioactive peptides. I. Distribution and molecular characteristics of two cardioacceleratory peptides in the tobacco hawkmoth, Manduca sexta. , 1985, The Journal of experimental biology.

[21]  W. Burggren,et al.  Developmental changes in in vivo cardiac performance in the moth Manduca sexta. , 2000, The Journal of experimental biology.

[22]  J. Putney,et al.  Capacitative calcium entry in the nervous system. , 2003, Cell calcium.

[23]  C. Franzini-armstrong,et al.  Formation of junctions involved in excitation-contraction coupling in skeletal and cardiac muscle. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Dc Washington,et al.  USEPA. Reregistration Eligibility Decision (RED): 738‐R‐99‐004. United States Environmental Protection Agency, Prevention, Pesticides and Toxic Substances (7508C): 337 pp. , 1999 .

[25]  G. Meissner,et al.  Ryanodine receptor/Ca2+ release channels and their regulation by endogenous effectors. , 1994, Annual review of physiology.

[26]  M. Zochowski,et al.  Distinct Intracellular Calcium Transients in Neurites and Somata Integrate Neuronal Signals , 2002, The Journal of Neuroscience.

[27]  R. Coronado,et al.  Structure and function of ryanodine receptors. , 1994, The American journal of physiology.

[28]  T. Miller,et al.  Neurochemical Techniques in Insect Research , 1985, Springer Series in Experimental Entomology.

[29]  A. Herrmann-Frank,et al.  The role of Ca2+ ions in excitation-contraction coupling of skeletal muscle fibres. , 1995, Biochimica et biophysica acta.

[30]  J. Casida,et al.  Similarity of insect and mammalian ryanodine binding sites , 1994 .

[31]  J. Casida,et al.  Ca2+-activated ryanodine binding: mechanisms of sensitivity and intensity modulation by Mg2+, caffeine, and adenine nucleotides. , 1987, Molecular pharmacology.

[32]  T. Hosoya,et al.  Isolation and characterization of a gene for a ryanodine receptor/calcium release channel in Drosophila melanogaster , 1994, FEBS letters.

[33]  H. Nakamura,et al.  9-methyl-7-bromoeudistomin D, a powerful radio-labelable Ca++ releaser having caffeine-like properties, acts on Ca(++)-induced Ca++ release channels of sarcoplasmic reticulum. , 1991, The Journal of pharmacology and experimental therapeutics.

[34]  Ming-Hsuan Yang,et al.  Calcium channel as a new potential target for insecticides. , 1995 .

[35]  T. Miller,et al.  8 – Structure and Physiology of the Circulatory System , 1985 .

[36]  A. Herrmann-Frank,et al.  4-Chloro-m-cresol, a potent and specific activator of the skeletal muscle ryanodine receptor. , 1996, Biochimica et biophysica acta.

[37]  P. Usherwood.  The action of the alkaloid ryanodine on insect skeletal muscle. , 1962, Comparative biochemistry and physiology.

[38]  D. Sattelle,et al.  Gene silencing of selected calcium-signalling molecules in a Drosophila cell line using double-stranded RNA interference. , 2004, Cell calcium.

[39]  S. Morris,et al.  Functional properties of Drosophila inositol trisphosphate receptors. , 2001, The Biochemical journal.

[40]  M. Londershausen,et al.  Binding Sites for Ca2+‐Channel Effectors and Ryanodine in Periplaneta americana—Possible Targets for New Insecticides , 1996 .

[41]  E. Harlow,et al.  Antibodies: A Laboratory Manual , 1988 .

[42]  J. Clark.  Molecular action of insecticides on ion channels. , 1995 .

[43]  D. Sattelle,et al.  Spatiotemporal calcium signaling in a Drosophila melanogaster cell line stably expressing a Drosophila muscarinic acetylcholine receptor , 2003, Invertebrate Neuroscience.

[44]  R. Hollingworth,et al.  Natural and Engineered Pest Management Agents , 1993 .

[45]  Z. J. Penefsky,et al.  The effects of ryanodine, acetylcholine and epinephrine on electrical and mechanical activity in an insect heart , 1981 .

[46]  M. Dekeyser.  Acaricide mode of action. , 2005, Pest management science.

[47]  F. Koniuszy,et al.  Plant insecticides; ryanodine, a new alkaloid from Ryania speciosa Vahl. , 1948, Journal of the American Chemical Society.

[48]  Michael Fill,et al.  Ryanodine receptor calcium release channels. , 2002, Physiological reviews.

[49]  M. Berridge,et al.  The versatility and universality of calcium signalling , 2000, Nature Reviews Molecular Cell Biology.

[50]  M. Estacion,et al.  Regulation of Drosophila TRPL Channels by Immunophilin FKBP59* , 2001, The Journal of Biological Chemistry.

[51]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[52]  M. Nishi,et al.  Molecular cloning of cDNA encoding a drosophila ryanodine receptor and functional studies of the carboxyl-terminal calcium release channel. , 2000, Biophysical journal.