Degenerative effects of 6-aminodopamine and 6-hydroxydopamine on peripheral adrenergic nerves.

Abstract

A 6-hydroxydopamine analogue, 6-aminodopamine (6-ADA), was compared with 6-hydroxydopamine (6-OHDA) as a potential agent for chemical sympathectomy. The adrenergic terminals innervating arterioles of the frog retrolingual membrane were used as a test system. Four days after two topical treatments with 0.25 mg/ml of either drug, most of the periarteriolar adrenergic nerves demonstrated swelling, fiber disruption, or a bright beaded appearance in the fluorescence microscope. Treatment with 0.5 mg/ml 6-OHDA abolished all fluorescence. After 0.5 mg/ml 6-ADA, no normal adrenergic fibers were seen, although a few fibers survived and exhibited a beaded appearance. In contrast to 6-OHDA, this higher dose of 6-ADA produced some signs of general tissue toxicity. After treatment with either drug, electron microscopy revealed adrenergic nerves with large electron-opaque structures containing the degenerated remains of large granular vesicles. Nerve areas which contained the degenerating structures occasionally alternated with swollen axonal regions containing many microtubules but no vesicles. Cholinergic nerves showed no evidence of damage. These results suggest that 6-ADA selectively destroys peripheral adrenergic nerves much like 6-OHDA, providing an additional marker for the ultrastructural identification of adrenergic nerves. Their analogous chemical suggest a similar metabolic mechanism for destruction of adrenergic nerves.