Stimulation of Melatonin Synthesis in Ovine Pineals In Vitro

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Abstract
Static and superfused pineal slices (750 .mu.m) have been used to study the control of melatonin synthesis by ovine pineals. Static incubates show a time-dependent accumulation of melatonin in the medium; this is significantly increased by stimulation with norepinephrine (NE) (10-5 M), reaching 300% above control levels after 4 h. Perifused pineal slices show a rapid rise in melatonin release within 12-18 min in response to NE stimulation. This reaches a 3.5-4.5-fold increase in melatonin released within 30 min. Withdrawal of NE is associated with a rapid return to prestimulated levels within 12-18 min. These time-course characteristics compare favorably to those changes seen in vivo. The formation of [14C]melatonin from [14C]-tryptophan shows a linear increase with time. In the presence of NE (10-5 M), the rate of synthesis is increased, albeit after an initial time lag of at least 30 min. The latter may reflect an N-acetyltransferase-independent mechanism of synthesis and release. In static incubations, propranolol (10-5 M) inhibited NE-induced melatonin production by about 60%, but prazosin (10-5 M) had no effect. As dibutyryl cyclic AMP (10-3 M) stimulated melatonin production, it is concluded that .beta.-receptors are of primary importance to the control of melatonin production, as in the rat. The role of .alpha.1-receptors is less clear, but the stimulatory action of phorbol 12-myristate 13-acetate on melatonin release implicates a receptor linked to phosphatidylinositol turnover.