The effect of acute acetaminophen administration on rat pineal indole metabolism

The pineal organ culture technique is invaluable in assessing the effects of drugs, which alter indoleamine synthesis. In the present study we used the rat pineal organ culture technique to determine the effects of acute high doses (100mg/kg every hour for three hours) on the synthesis of hydroxy and methoxy indoles using radiolabelled tryptophan as a precursor. Acetaminophen at this dosage has been shown to increase rat forebrain serotonin levels with a concomitant inhibition of rat liver tryptophan-2,3-dioxygenase activity. The results show that acetaminophen administration significantly (p <0.05) increased the conversion of radiolabelled tryptophan to radiolabelled melatonin compared to controls. The reason for the increased synthesis of melatonin could be due to inhibition of the release of the precursors of melatonin from the pinealocytes or it could be due to possible effects of high doses of this drug on the pineal P-adrenoceptor complex. It is unlikely that the increased melatonin is due to the rise in forebrain serotonin levels induced by acetaminophen since changes in forebrain serotonin levels do not alter pineal serotonin concentrations. The mechanism by which acetaminophen increases melatonin synthesis in the pineal gland needs to be investigated.