Catecholamine synthesis inhibitors increase pineal adrenaline content by stimulating adrenal medullary activity

Estimation of noradrenaline and adrenaline utilization in the pineal gland of female rats was attempted using inhibitors of the enzymes that catalyse the catecholamine biosynthetic pathway. Treatment with FLA63, an inhibitor of dopamine beta-hydroxylase (10 mg/kg, 2 h before killing), induced depletion of noradrenaline and adrenaline in the preoptic area and median eminence (sites, respectively, inside and outside the blood-brain barrier) but, paradoxically, resulted in a significant increase (+77%) in the pineal content of adrenaline without affecting that of noradrenaline. Treatment with LY134046, an inhibitor of phenylethanolamine N-methyltransferase (40 mg/kg, 5 and 2 h before killing), induced depletion of adrenaline in the preoptic area and median eminence but, again, resulted in a paradoxical and large increase in pineal adrenaline (+224%); this increase was prevented by prior adrenalectomy. Blood samples taken from free-moving rats fitted with intravenous and intraperitoneal cannulae revealed a marked increase in plasma levels of adrenaline after each injection of LY134046. These results suggest that the adrenal medulla is the primary source for the increase in pineal adrenaline seen after administration of the enzyme inhibitors. The precise site of uptake and the biological implications of this phenomenon remain to be elucidated. Nevertheless, interpretation of in vivo experiments involving these catecholamine synthesis inhibitors should take this adrenal response into account.