MECHANISMS OF RYANODINE TOXICITY

Information

  • Research Project
  • 3304215
  • ApplicationId
    3304215
  • Core Project Number
    R01GM044896
  • Full Project Number
    1R01GM044896-01A1
  • Serial Number
    44896
  • FOA Number
  • Sub Project Id
  • Project Start Date
    1/6/1992 - 32 years ago
  • Project End Date
    1/5/1995 - 29 years ago
  • Program Officer Name
  • Budget Start Date
    1/6/1992 - 32 years ago
  • Budget End Date
    1/5/1993 - 31 years ago
  • Fiscal Year
    1992
  • Support Year
    1
  • Suffix
    A1
  • Award Notice Date
    1/3/1992 - 32 years ago
Organizations

MECHANISMS OF RYANODINE TOXICITY

Ryanodine, a lipid soluble plant alkaloid, is a powerful inhibitor of contractions of vertebrate and insect muscles. In both vertebrates and insects it influences Ca2+ sequestration mechanisms of muscle sarcoplasmic reticulum. In insects it also profoundly influences the electrical excitability of skeletal muscle, probably by changing the ion transport specificities of voltage-sensitive K+ channels. Ryanodol and 2,19-didehydroryanodol are two analogues of ryanodine which are insect specific poisons. The major objective will be to establish the basis for this insect specificity using a variety of electrophysiological approaches involving whole animals through to single channels and by comparing the effects of these compounds on the excitability of insect and mammalian skeletal muscle. These studies will test the hypothesis that ryanodol and 2,19-didehydroryanodol knock down insects by targeting only the surface (excitable) membrane of insect muscle. Another objective is to study the effects of ryanodine and analogues on Na+, Ca2+ , and K+ and Cl- channels in the excitable membrane of locust skeletal muscle and, thereby, gain further insight into the molecular basis for ryanodine poisoning of insects. A limited structure-activity study, initially involving ryanodine and three analogues, will provide insight into the structural requirements for optimal interaction of ryanoids with insect muscle membrane and, thereby, provide opportunities for future rational synthesis of highly focussed, insect specific toxicants. The long-term objective of this work is to point to chemicals which have high potency in pest insects but low toxicity to vertebrates and, perhaps, other invertebrates.

IC Name
NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
  • Activity
    R01
  • Administering IC
    GM
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
  • Sub Project Total Cost
  • ARRA Funded
  • CFDA Code
    859
  • Ed Inst. Type
  • Funding ICs
  • Funding Mechanism
  • Study Section
    TOX
  • Study Section Name
    Toxicology Study Section
  • Organization Name
    UNIVERSITY OF NOTTINGHAM
  • Organization Department
  • Organization DUNS
  • Organization City
    NOTTINGHAM
  • Organization State
  • Organization Country
    UNITED KINGDOM
  • Organization Zip Code
    NG7 2RD
  • Organization District
    UNITED KINGDOM