Jaffar,, Zeina Hassan; (1991) Some studies on the effect of adenosine 5'-triphosphate (ATP) on mast cells. Doctoral thesis (Ph.D.), University College London.

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Abstract

Exogenous ATP has long been known to induce the exocytotic release of histamine from rat peritoneal mast cells. The nucleotide is thought to act through specific receptors by inducing the formation of lesions in the cell membrane which permit the influx of extracellular calcium ions and thereby initiate secretion. The present study demonstrates some further characteristics of this effect. ATP induced a dose-dependent release of histamine and prostaglandin D2 from rat serosal mast cells. The release process was relatively slow, non-cytotoxic, optimal at physiological pH and completely dependent on external calcium. At high concentrations, strontium and barium ions could substitute for calcium. The action of ATP was highly tissue and species selective. In particular, tissue mast cells from the guinea pig and man were totally unresponsive. This study has also shown that viable and functional mast cells may be isolated from the rat urinary bladder. The bladder cells were responsive to a variety of diverse stimuli including the nucleotide. In addition, ATP was employed as a cell permeabilizing tool for introducing certain intracellular effectors into the cytosol of rat mast cells, in an attempt to probe internal events leading to histamine release. Secretion evoked by ATP was largely unaffected by antiasthmatic chromones but was inhibited by structurally related flavonoids and cyclic AMP-active drugs. Use of appropriate agonists and antagonists indicated that the effects of ATP on rat mast cells were not mediated through classical purinergic receptor subtypes as defined from smooth muscle studies. ATP thus appears to act through a novel purinoceptor or binding site present on certain types of mast cells.

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