Noradrenergic lesioning with an anti-dopamine beta-hydroxylase immunotoxin.
Sympathectomy has been achieved by a variety of methods but each has its limitations. These include lack of tissue specificity, incomplete lesioning, and the age range of susceptibility to the lesioning. To circumvent these drawbacks, an immunotoxin was constructed using a monoclonal antibody against the noradrenergic specific enzyme dopamine beta-hydroxylase (D beta H) coupled via a disulfide bond to saporin, a ribosomal inactivating protein. Three days after intravenous injection of the anti-D beta H immunotoxin (50 micrograms) into adult Sprague-Dawley rats, 66% of neurons in the superior cervical ganglia were chromatolytic. Superior cervical ganglia neurons were poisoned in 1 day old and 1 week old (86% of neurons) neonatal rats following subcutaneous injection of 3.75 and 15 micrograms, respectively. The anti-D beta H immunotoxin will be a useful tool in the study of the peripheral noradrenergic system in adult and neonatal animals.
Picklo
M J
MJ
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232.
Wiley
R G
RG
Lappi
D A
DA
Robertson
D
D
D000818:Animals; D000911:Antibodies, Monoclonal; D048588:Benzoxazines; D004396:Coloring Agents; D004299:Dopamine beta-Hydroxylase / Q000276:immunology* / Q000378:metabolism*; D005728:Ganglia, Sympathetic / Q000187:drug effects; D000922:Immunotoxins / Q000276:immunology* / Q000494:pharmacology*; D008297:Male; D009699:N-Glycosyl Hydrolases; D009638:Norepinephrine / Q000378:metabolism*; D010078:Oxazines; D010940:Plant Proteins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013563:Sympathectomy, Chemical / Q000379:methods*
D000911:Antibodies, Monoclonal; D048588:Benzoxazines; D004396:Coloring Agents; D000922:Immunotoxins; D010078:Oxazines; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C101397:anti-dopamine beta-hydroxylase immunotoxin; C028911:cresyl violet; D004299:Dopamine beta-Hydroxylase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D009638:Norepinephrine