ANTI-DOPAMINE BETA-HYDROXYLASE IMMUNOTOXIN-INDUCED SYMPATHECTOMY IN ADULT-RATS

Anti-dopamine beta-hydroxylase immunotoxin (DHIT) is an antibody-targe ted noradrenergic lesioning tool comprised of a monoclonal antibody ag ainst the noradrenergic enzyme, dopamine beta-hydroxylase, conjugated to saporin, a ribosome-inactivating protein. Noradrenergic-neuron spec ificity and completeness and functionality of sympathectomy were asses sed. Adult, male Sprague-Dawley rats were given 28.5, 85.7, 142 or 285 mu g/kg DHIT i.v. Three days after injection, a 6% to 73% decrease in the neurons was found in the superior cervical ganglia of the animals . No loss of sensory, nodose and dorsal root ganglia, neurons was obse rved at the highest dose of DHIT. In contrast, the immunotoxin, 192-sa porin (142 mu g/kg), lesioned all three ganglia. To assess the sympath ectomy, 2 wk after treatment (285 mu g/kg), rats were anesthetized wit h urethane (1 g/kg) and cannulated in the femoral artery and vein. DHI T-treated animals' basal systolic blood pressure and heart rate were s ignificantly lower than controls. Basal plasma norepinephrine levels w ere 41% lower in DHIT-treated animals than controls. Tyramine-stimulat ed release of norepinephrine in DHIT-treated rats was 27% of controls. Plasma epinephrine levels of DHIT animals were not reduced. DHIT-trea ted animals exhibited a 2-fold hypersensitivity to the cr-adrenergic a gonist phenylephrine. We conclude that DHIT selectively delivered sapo rin to noradrenergic neurons resulting in destruction of these neurons . Anti-dopamine beta-hydroxylase immunotoxin administration produces a rapid, irreversible sympathectomy.