Effect of melatonin on [H-3]-phorbol dibutyrate binding to kinase C protein

Melatonin is a highly lipophylic compound that acts mainly on the Central Nervous System (CNS). Evidence suggesting that the hormone may be involved in psychiatric diseases is growing. However, the precise role of melatonin as well as its usefulness in CNS diseases remain to be elucidated. Currently it is known that melatonin acts as a free radical scavenger and through binding to membranal receptors, calmodulin and nuclear proteins. Melatonin binds to calmodulin and acts as a potent calmodulin antagonist both in vitro and in vivo. Moreover, recently we described that melatonin activates protein kinase C, a family of eleven isoenzymes that play a key role in cellular physiology. The enzyme has a hydrophobic binding site where activators (diacylglycerol and phorbol esters) bind. In addition, the group A of protein kinase C isoenzymes are activated in the presence of Ca++. In this work we explored the effects of melatonin on phorbol ester H-3-Phorbol, 12,13 dibutirate binding. The results showed that melatonin increased the H-3-PDBu binding to the enzyme by 50 % in the presence of calcium. All indoles tested were ineffective at 1 nM. The results show that besides melatonin binding to calmodulin, the hormone also interacts with protein kinase C and those mechanisms can modify cellular physiology through protein phosphorylation. The results also suggest that intracellular actions of MEL may involve interactions with another hydrophobic and calcium dependent proteins.