Lowered norepinephrine turnover as a sign of impaired ganglionic transmission after preganglionic lesioning by acetylcholinesterase antibodies.
Monoclonal antibodies to acetylcholinesterase are known to destroy preganglionic sympathetic terminals in rats. To investigate resulting changes in sympathetic tone, turnover of norepinephrine (NE) was examined in five adrenergically innervated tissues: submaxillary salivary gland, heart, spleen, vas deferens and kidney. At time zero, 50 mu Ci of [3H]NE was injected into the tail vein; turnover rates were determined from the loss of radioactive NE between 2 and 24 hr later. Experiments with ganglionic blocking agents showed that most NE turnover was related to impulse traffic. Combined treatment with atropine (4 mg/kg/day) and chlorisondamine (20 mg/kg/day) reduced the apparent turnover rate constant by two thirds or more in all organs except vas deferens. NE turnover was likewise slowed after treatment with acetylcholinesterase antibodies (1.6 mg i.v., 5 days earlier): apparent rate constants fell 50% or more in submaxillary gland, heart and kidney. The reduced NE turnover in these end organs suggested that preganglionic immunologic lesions blocked synaptic transmission in the respective sympathetic ganglia. Sustained turnover in the spleen, however, suggested that certain pathways through the celiac ganglion resisted immunologic lesion or recovered quickly. Hence, there may be structural or functional differences among the sympathetic ganglia, especially between pre- and paravertebral groups.
McKinzie
S
S
Department of Pharmacology, Mayo Clinic, Rochester, Minnesota, USA.
Tyce
G M
GM
Brimijoin
S
S
D000110:Acetylcholinesterase / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D003080:Cold Temperature; D005728:Ganglia, Sympathetic / Q000502:physiology*; D005730:Ganglionic Blockers / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission
D000911:Antibodies, Monoclonal; D005730:Ganglionic Blockers; D000110:Acetylcholinesterase; D009638:Norepinephrine