Application of a membrane fusion assay for rapid drug screening.
OBJECTIVE
The purpose of this study is to develop an in vitro assay for screening drug and their effects on membrane fusion and lysis of intracellular organelles.


METHODS
A 96-well microtiter-dish turbidimetric assay using membrane components of the eggs of sea urchins, a marine invertebrate, was applied to monitor granule fusion and/or lysis.


RESULTS
Of 18 drugs screened, 16 had no effect. One antineoplastic drug, tamoxifen, disrupted intracellular membranes in a calcium independent manner. Taxol, another antineoplastic drug, specifically inhibited calcium triggered exocytosis.


CONCLUSIONS
This assay is inexpensive, simple, rapid, and does not require the sacrifice of animal life. It has the potential to identify drugs that are membrane active, as well as those which specifically perturb events involved in the secretion process.
Vogel
S S
SS
Laboratory of Theoretical and Physical Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Beushausen
S
S
Lester
D S
DS
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005089:Exocytosis; D008561:Membrane Fusion; D012617:Sea Urchins
D002118:Calcium