Melatonin modulates acid/base transport in human pancreatic carcinoma cells.
Melatonin was found to improve pancreatic organ function in diseased animals. To study whether pancreatic bicarbonate secretion is stimulated by melatonin, investigations were done in two human ductal pancreatic adenocarcinoma cell lines MIA PaCa-2 (MIA) and PANC-1 (PANC). Using the fluorescence pH-sensor BCECF-AM, we monitored melatonin effects on basal intracellular pH (pH(i)), and on pH(i) recovery after intracellular alkalinization produced by the removal of extracellular HCO(3) (-)/CO(2). Exposure to 1 microM melatonin for 24 hrs and presence of the indoleamine during the experiment increases the basal pH(i). Moreover, pHi recovery and HCO(3) (-) secretion are facilitated after the alkaline load. These findings are in line with the observed increase in mRNA expression of the Na(+)/HCO(3) (-)-cotransporter SLC4A4b for the uptake and the Cl(-)/HCO(3) (-)-exchanger SLC26A6 for the secretion of HCO(3) (-). The reduction in Na(+)/H(+)- exchanger SLC9A1 mRNA would favor pH(i) recovery after alkalinization, but it does not explain the initial increase in pHi. This controversial effect and the requirement for continuous presence of melatonin throughout the experiment suggest that nontranscriptional signalling may contribute to the effects of melatonin on acid/base movements. In summary, we show a stimulatory effect of melatonin on bicarbonate secretion in the pancreatic cancer cell lines which may help to prevent duodenal damage.
Aust
Sylvia
S
Department of Pathophysiology, Center for Physiology and Pathophysiology, Vienna General Hospital, Vienna, Austria.
Brucker
Brigitte
B
Graf
Jürg
J
Klimpfinger
Martin
M
Thalhammer
Theresia
T
D000143:Acids / Q000378:metabolism*; D017920:Antiporters / Q000235:genetics; D001639:Bicarbonates / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008550:Melatonin / Q000494:pharmacology*; D008954:Models, Biological; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044122:Receptor, Melatonin, MT1 / Q000235:genetics; D044123:Receptor, Melatonin, MT2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics
D000143:Acids; D017920:Antiporters; D001639:Bicarbonates; D012333:RNA, Messenger; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D027981:Symporters; D005576:Colforsin; D000242:Cyclic AMP; D008550:Melatonin