Ryanodine receptors in peritoneal mast cells: possible role in the modulation of exocytotic activity.

Previous studies have shown that ryanodine in low concentrations and caffeine increase intracellular [Ca(2+)] in the absence of external Ca(2+), suggesting Ca(2+) release from intracellular stores through ryanodine receptors (RyR). In the present study we employed amperometry to examine the effect of RyR agonists and antagonists on serotonin release elicited with compound 48/80 (10 micro g/ml). Ryanodine (1 micro M) or, similarly, 20 mM caffeine, in the absence of external Ca(2+), enhanced the amperometric response to compound 48/80 and all the individual amperometric spike parameters. Ryanodine (50 micro M), dantrolene (20 micro M) and tetracaine (50 micro M), putative antagonists of the RyR, attenuated the amperometric response significantly, decreasing the number and frequency of events as well as their amplitude. This is the first demonstration that Ca(2+) availability from RyR-operated Ca(2+) sources may contribute to the modulation of secretory activity in mast cells, affecting not only the cellular exocytotic response, but also the characteristics of single amperometric events. Immunocytochemical labelling, using a monoclonal RyR antibody, confirmed the presence of RyR in this preparation.