Melatonin induced cyclic modulation of vectorial water transport in kidney-derived MDCK cells.

BACKGROUND

Melatonin, newly synthesized by the pineal gland, is rapidly released to general circulation reaching a nanomolar concentration. Cyclic production of melatonin synchronizes body rhythms with the photoperiod. Moreover, changes in urine production and osmolarity have been observed in the kidney during the night. However, the precise mechanisms by which plasma-circulating melatonin modifies renal physiology are not clearly understood.

METHODS

Madin-Darby canine kidney (MDCK) cell monolayers transport water vectorially from the apical to the basolateral side forming blisters or domes. Transport in epithelial cells is regulated by tight junction sealing, ion pumps and channels, and cytoskeleton organization, among other processes. MDCK cells were used to study vectorial water transport to determine the role of microfilament organization and protein kinase C (PKC) in dome formation in culture conditions that mimic the cyclic pattern of melatonin circulation in plasma.

RESULTS

Melatonin cyclically increased dome formation by 50% and caused enlargement and thickening of stress fibers in cells surrounding the domes. Optimal increase in dome formation was observed at nanomolar concentrations of melatonin after 6 hours, concomitantly with a 28% decrease in the transepithelial electrical resistance, which remained low for up to 12 hours, without apparent change in fluorescein isothiocyanate (FITC)-dextran flux. A blockage in dome formation elicited by melatonin was observed in monolayers preincubated with the Na+-K+-ATPase or PKC inhibitors.

CONCLUSION

The results obtained indicate that melatonin cyclically modifies the transepithelial permeability in kidney-derived cells through PKC activation and microfilament reorganization, and supports the hypothesis that melatonin may synchronize daily body rhythms through cyclic cytoskeletal rearrangements.