Abstract— This investigation was designed to determine whether the amount of serotonin (5‐HT) in cultured pineal glands can be altered by norepinephrine (NE). Treatment with l‐NE (10−5‐10−7m) for 4‐6 h caused a gradual decrease in the concentration of 5‐HT to a value that was less than 30% of that in the untreated control gland. This effect was observed using chronically denervated pineal glands. d‐Norepinephrine (10−6‐10−7m) and dopamine (10−4m) were ineffective in lowering 5‐HT. The effect of l‐NE was completely blocked by a β‐adrenergic receptor blocker, propranolol and was only slightly decreased by α‐adrenergic receptor blockers. These observations indicate that l‐NE acts post‐synaptically via a highly specific β‐adrenergic mechanism. The effect of l‐norepinephrine was mimicked by theophylline and N6, 2′0‐dibutyryl adenosine 3′,5′‐monophosphate, an indication that adenosine 3′,5′‐monophosphate is involved in the effect of l‐NE on 5‐HT. Treatment with cycloheximide, which by itself caused a decrease in pineal 5‐HT, also blocked any further decrease caused by treatment with l‐NE, an indication that protein synthesis is necessary for maintenance of baseline levels of serotonin and for the effect of l‐NE to be observed. The total amount of l‐[3H]NE and degradation products of L‐[3H]NE in the gland after 6 h of treatment with l‐[3H]NE was less than 3 pmol. This amount of l‐NE and degradation products of l‐NE could not account for the decrease of 100‐200 pmol of 5‐HT on the basis of a mole for mole replacement of 5‐HT by l‐NE. These findings are consistent with the hypothesis that non‐neuronal pineal 5‐HT is physiologically regulated by the release of l‐NE from the sympathetic nerve network.
Read full abstract