Melatonin Modulates Acid/Base Transport in Human Pancreatic Carcinoma Cells

Abstract

Melatonin was found to improve pancreatic organfunction in diseased animals. To study whetherpancreatic bicarbonate secretion is stimulated bymelatonin, investigations were done in two humanductal pancreatic adenocarcinoma cell lines MIAPaCa-2 (MIA) and PANC-1 (PANC). Using thefluorescence pH-sensor BCECF-AM, we monitoredmelatonin effects on basal intracellular pH (pH_i), andon pH_i recovery after intracellular alkalinizationproduced by the removal of extracellular HCO₃^-/CO₂.Exposure to 1µM melatonin for 24hrs and presenceof the indoleamine during the experiment increasesthe basal pH_i. Moreover, pHi recovery and HCO₃^-secretion are facilitated after the alkaline load. Thesefindings are in line with the observed increase in mRNAexpression of the Na⁺/HCO₃^--cotransporter SLC4A4bfor the uptake and the Cl^-/HCO₃^--exchanger SLC26A6for the secretion of HCO₃^-. The reduction in Na⁺/H⁺-exchanger SLC9A1 mRNA would favor pH_i recoveryafter alkalinization, but it does not explain the initialincrease in pHi. This controversial effect and therequirement for continuous presence of melatoninthroughout the experiment suggest that nontranscriptionalsignalling may contribute to the effectsof melatonin on acid/base movements. In summary,we show a stimulatory effect of melatonin onbicarbonate secretion in the pancreatic cancer celllines which may help to prevent duodenal damage.