ATP (as the tetrabasic acid, ATP4-) applied externally to rat mast cells causes the formation of lesions which permit influx and efflux of low molecular weight, normally impermeant aqueous solutes. To monitor membrane permeabilisation we have used two fluorescent dyes, ethidium which stains the nucleus, and TMA-DPH which stains the cytosolic surfaces of intracellular membranes following entry into the cells Permeabilisation by ATP is not affected by the metabolic status of the cells, and is maintained at temperatures as low as 8 degrees C. We have tested the ability of 30 structural analogues of ATP to effect mast cell permeabilisation. The analogues include those having substituents in the 2- and 8-positions of the purine ring, structural and optical isomers of the ribose sugar, and variations in the triphosphate chain. The pattern of selectivity displayed by the rat mast cell ATP4- receptor is distinct from those characteristic of the P1 purinoceptor for adenosine and the P2X and P2Y purinoceptors for adenine nucleotides.
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