Pharmacogenetics: defining the genetic basis of drug action and inositol trisphosphate analysis.
Medicinal drugs do not always have clearly understood mechanisms of action, especially as regards psychiatric treatment. Identification of genes involved in drug resistance is an important step toward elucidating the genetic basis of disease and the molecular mechanism of drug action. However, this approach is impractical in higher animals, as ablation and screening of every gene in an animal is not currently possible. Dictyostelium has proven a good model system for molecular pharmacological research as a result of its genetic tractability, ease of gene knockout, and creation of isogenic lines. In this system, we have identified genes that confer resistance to bipolar disorder drugs. This work has implicated inositol (1,4,5) trisphosphate (InsP3) signaling as a common mechanism of action for these drugs in patients.
Adley
Kathryn E
KE
Department of Biology, University College London, UK.
Keim
Melanie
M
Williams
Robin S B
RS
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics; D004251:DNA Transposable Elements; D004023:Dictyostelium / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance / Q000235:genetics*; D017353:Gene Deletion; D018390:Gene Targeting; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis*; D010597:Pharmacogenetics; D015183:Restriction Mapping
D018692:Antimanic Agents; D004251:DNA Transposable Elements; D015544:Inositol 1,4,5-Trisphosphate