Rediocide A, an Insecticide, induces G-protein-coupled receptor desensitization via activation of conventional protein kinase C.
In order to identify small-molecule antagonists of Methuselah (Mth), a Drosophila G-protein-coupled receptor (GPCR) involved in life-span control, a library of natural compounds was screened, and it was found that rediocide A (1), a daphnane ester from the roots of Trigonostemon reidioides and used currently for flea control, potently inhibited calcium mobilization mediated by this receptor. Compound 1 inhibited calcium mobilization in GPCRs other than Mth, indicating that the inhibitory effect was not due to receptor antagonism but rather to a more general mechanism. It was found that 1 can induce GPCR desensitization and internalization, and such effects were mediated by the activation of conventional protein kinase C.
State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
Lixin
L
Cui
Jing
J
Li
Xin
X
Xie
D000818:Animals; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000187:drug effects; D007306:Insecticides / Q000737:chemistry / Q000494:pharmacology*; D018942:Macrolides / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism*
D004224:Diterpenes; D029721:Drosophila Proteins; D007306:Insecticides; D018942:Macrolides; D043562:Receptors, G-Protein-Coupled; C115381:mth protein, Drosophila; C483695:rediocide A; C011309:mezerein; D011493:Protein Kinase C