Melatonin induces calcium release from CCK‐8‐ and thapsigargin‐sensitive cytosolic stores in pancreatic AR42J cells

Abstract: Melatonin is produced following circadian rhythm with high levels being released at night and has been implicated in the regulation of physiological processes in major tissues, including the pancreas. The aim of our study was to examine the effects of melatonin on intracellular free Ca²⁺ concentration ([Ca²⁺]_c) in AR42J pancreatic cells. Our results show that stimulation of cells with 1 nm cholecystokinin (CCK)‐8 led to a transient increase in [Ca²⁺]_c followed by a decrease towards a value close to the prestimulation level. Melatonin (at the concentrations 1, 10, 100 μm and 1 mm ) induced changes in [Ca²⁺]_c that consisted of single or short lasting spikes in the form of oscillations or slow transient increases followed by a slow reduction towards a value close to the resting level. Depletion of intracellular Ca²⁺ stores by stimulation of cells with 1 nm CCK‐8 or 1 μm thapsigargin (Tps) blocked Ca²⁺ responses evoked by melatonin in the majority of cells. Conversely, prior stimulation of cells with 1 mm melatonin in the absence of extracellular Ca²⁺ inhibited Ca²⁺ mobilization in response to a secondary application of CCK‐8 or Tps. In summary, our results show that melatonin releases Ca²⁺ from intracellular stores and can therefore modulate the responses of the pancreas to CCK‐8. The source for Ca²⁺ mobilization most probably is the endoplasmic reticulum. These data raise the possibility that melatonin also involves Ca²⁺ signalling, in addition to other intracellular messengers, to modulate cellular function.