Melatonin induces calcium release from CCK-8- and thapsigargin-sensitive cytosolic stores in pancreatic AR42J cells.
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 Ca(2+) concentration ([Ca(2+) ](c)) in AR42J pancreatic cells. Our results show that stimulation of cells with 1 nm cholecystokinin (CCK)-8 led to a transient increase in [Ca(2+) ](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 [Ca(2+) ](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 Ca(2+) stores by stimulation of cells with 1 nm CCK-8 or 1 μm thapsigargin (Tps) blocked Ca(2+) responses evoked by melatonin in the majority of cells. Conversely, prior stimulation of cells with 1 mm melatonin in the absence of extracellular Ca(2+) inhibited Ca(2+) mobilization in response to a secondary application of CCK-8 or Tps. In summary, our results show that melatonin releases Ca(2+) from intracellular stores and can therefore modulate the responses of the pancreas to CCK-8. The source for Ca(2+) mobilization most probably is the endoplasmic reticulum. These data raise the possibility that melatonin also involves Ca(2+) signalling, in addition to other intracellular messengers, to modulate cellular function.
del Castillo-Vaquero
Angel
A
Department of Physiology (Cell Physiology Research Group), University of Extremadura, Caceres, Spain.
Salido
Gines M
GM
Gonzalez
Antonio
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D012844:Sincalide / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
D000975:Antioxidants; D004791:Enzyme Inhibitors; D019284:Thapsigargin; D008550:Melatonin; D012844:Sincalide; D002118:Calcium