Diurnal changes in cyclic nucleotide response to pineal indoles in murine mammary glands

The aim of this study was to determine whether pineal indoles affect cyclic nucleotide levels in mammary gland slices of BALB/c adult mice. Melatonin at 0.1 nM-10 microM concentrations decreased cAMP and augmented cGMP concentration in murine mammary gland slices in the presence of a phosphodiesterase inhibitor (1 mM theophylline), an index of cyclic nucleotide synthesis. Melatonin-induced changes in cyclic nucleotide levels were significantly larger at the end of the light period (2000) than in the morning (at 1000). Indole-induced inhibition of cyclic AMP levels by mammary slices exhibited the following order of potency: 5-methoxytryptamine > melatonin > or = 6-hydroxymelatonin > serotonin, N-acetylserotonin > 5-hydroxytryptophol. The order of potency for indole-induced augmentation of cyclic GMP levels was: 5-methoxytryptamine > melatonin > 6-hydroxymelatonin > serotonin, N-acetylserotonin, 5-hydroxytryptophol. When melatonin or 5-methoxytryptamine (10 nM) were examined for their effects on cAMP and cGMP levels in mammary glands of mice killed at six different time intervals during the 24-hr cycle, the activity was maximal during night. The data demonstrate that 5-methoxytryptamine and melatonin decreased cAMP and increased cGMP levels in mammary gland slices. Methoxyindole-induced changes in cyclic nucleotide synthesis in murine mammary glands exhibit the time-dependency known to occur in several other melatonin-influenced responses.