Docosahexaenoic acid reduces both cyclic nucleotide and melatonin synthesis in rat pinealocytes.

The effect of docosahexaenoic acid (22:6n-3) on melatonin (MT) production in rat pinealocytes was measured. In pinealocytes, supplementation with 50 microM 22:6n-3 for 48 h decreased MT production after a norepinephrine (NE)-stimulation (1 and 10 microM). Using co-treatment with IBMX (1 mM), a cyclic nucleotide phosphodiesterase inhibitor known to increase NE-stimulated cAMP and prazosin (1 microM), an alpha 1 antagonist, the results indicate that a) 22:6n-3 did not act on cyclic nucleotide phosphodiesterase activities to decrease both cAMP (-64%) and cGMP (-45%) levels and b) the inhibition of cGMP was higher (-70%) in presence of prazosin. These results confirm that in rat pinealocytes the lowering effect of 22:6n-3 supplementation on cAMP is likely to be dependent on alpha 1-adrenoceptor modulation whereas the decrease of cGMP seems to involve other intracellular mechanisms. The absence of 22:6n-3 effect on serotonin metabolites suggest that the lowering effect on MT may be also correlated with alterations of O-methylation step.