A Novel Aspect of Photodynamic Action: Induction of Recurrent Spikes in Cytosolic Calcium Concentration

Effects of photodynamic action of gadolinium porphyrin-like macrocycle B (PLMGdB) on cytosolic Ca²⁺ concentration, Ca²⁺]_c, was investigated in isolated rat pancreatic acini. The PLMGdB alone or light alone (2 min) had no effect on Ca²⁺]_c. Cell-bound PLMGdB upon brief (0.5–2.0 min) light activation triggered recurrent spikes in Ca²⁺]_c. At lower PLMGdB concentration (100 nM) the spikes continued during the whole period of monitoring Ca²⁺]_c. At a higher concentration of 500 nM, the spikes continued for the first 40 min, followed by a gradual increase in basal Ca²⁺]_c upon which smaller spikes were superimposed. At 1, the spikes continued for the first 20 min, after that spiking gradually degenerated into a plateau phase. In many aspects, photodynamically triggered spikes resembled spikes generated by physiological concentrations of cholecystokinin. The spikes triggered by photodynamic action were likely to be the result of the ignition of a physiological “chain reaction”, because functional inositol-1,4,5-trisphosphate (IP₃) receptors were required for spiking to occur. Two-aminoe-thoxydiphenylborate, an inhibitory modulator of IP₃-triggered Ca²⁺ release from intracellular stores, effectively inhibited photodynamically generated spikes. Therefore photodynamic action appears to be able to permanently transfix a physiological process, leading to long-lasting pharmacological or therapeutic effects.