NOREPINEPHRINE, UNLIKE ATP, INDUCES ALL-OR-NONE INCREASE IN CYTOSOLIC CALCIUM IN THYROID-CELLS - THE ROLE OF INOSITOL-TRISPHOSPHATE-SENSITIVE STORES AND CALCIUM CHANNELS

The mechanism of action of norepinephrine and ATP has been analyzed in single FRTL5 cells (a normal thyroid cell line), loaded with the fluorescent Ca2+ probe Fura2. ATP increased the cytosolic Ca2+ in an apparently concentration-dependent manner with a maximal effect at 10 mu M (413+/-26% over basal levels of 135+/-7 nM). In contrast, the norepinephrine-induced increase (198+/-5% over basal) was concentration independent in individual cells, the minimal effective concentration being 1 nM. However, the number of cells responding to norepinephrine was concentration dependent. The ATP-induced Ca2+ rise was biphasic, consisting of a rapid rise (2-4 s, 252+/-15%), resembling the effect of norepinephrine, followed by a slower and longer component, which reached a plateau in 0.5-2 min. The second component appeared to be related to the opening of a channel, since it required extracellular Ca2+ and was abolished by SC38249, an inhibitor of the second-messenger-operated and voltage-operated channels. Moreover, it was inhibited by 4 beta-phorbol 12-myristate 13-acetate, suggesting that protein kinase C might be involved in the modulation of this Ca2+ channel.