INTERACTION OF FORSKOLIN AND MELATONIN ON CYCLIC-AMP GENERATION IN PARS TUBERALIS CELLS OF OVINE PITUITARY

The pineal indoleamine, melatonin, acts on specific secretory cells of the pars tuberalis of the sheep pituitary. Using pars tuberalis cells in primary culture melatonin inhibited forskolin-stimulated cyclic AMP production in both a time- and dose-dependent manner, but the nature of the melatonin response was critically dependent upon the stimulatory concentration of forskolin used. Forskolin alone stimulated dose-dependent cyclic AMP accumulation, which reached an equilibrium state after 15 min. This was maintained for up to 3 h, indicating a lack of desensitization to forskolin. Melatonin (1-mu-M) inhibited this response by greater than 80% at all doses. However, 100-mu-M forskolin reduced both the affinity and the number of the melatonin receptors, relative to untreated controls. Consistent with this, melatonin was 100 times less potent at inhibiting forskolin-stimulated cyclic AMP production, when titrated against 100-mu-M forskolin as compared to 1-mu-M forskolin. The response to 1-mu-M forskolin could be potentiated by 10-mu-M phorbol 12,13 myristate acetate, but not by calcium ionophore (A23187). This provides evidence for the interaction of the phosphatidylinositol pathway with the cyclic AMP system in these cells. Nevertheless melatonin can inhibit both the potentiated and non-potentiated response with equal effect.