UPTAKE AND ACCUMULATION OF ³H-6,7-DIHYDROXY-TETRAHYDROISOQUINOLINE BY PERIPHERAL SYMPATHETIC NERVES IN VIVO

¹ Parkinson's Disease Research Center, College of Physicians and Surgeons, Columbia University, and The New York State Psychiatric Institute, New York, New York

³H-6,7-dihydroxytetrahydroisoquinoline was prepared by condensation of ³H-dopamine with formaldehyde. When administered intravenously, this ³H-alkaloid was taken up into the mouse heart and into the submaxillary glands and irides of rats. Additionally, uptake into adrenal glands was also observed. Confirmation that uptake was into sympathetic nerve terminals of the heart was achieved by experiments with chemically denervated (6-hydroxydopamine-treated) mice, and by use of catecholamine uptake inhibitors (cocaine and desmethylimipramine). These treatments diminished uptake of the ³H-alkaloid into the heart by 48 to 79%. Similarly, uptake specifically into nerve terminals of the iris and submaxillary gland was identified in experiments with surgically denervated rats (unilateral superior cervical ganglionectomy). Denervation reduced the ³H-alkaloid by 75 to 84% in the iris and by 39 to 53% in the submaxillary gland. The ³H-alkaloid in aluminum hydroxide-purified extracts of tissues was identified by thinlayer chromatography. In denervated preparations, or after cocaine or desmethylimipramine, the ³H-alkaloid was more extensively metabolized. Neuronal ³H-alkaloid was relatively protected from metabolic transformation. The relationship of these observations to a hypothesis about tetrahydroisoquinoline biosynthesis from endogenous catecholamines during ethanol metabolism is discussed.