Effects of colchicine application to preganglionic axons on choline acetyltransferase activity and acetylcholine content and release in the superior cervical ganglion.
These experiments investigate the effect of block, by colchicine, of fast axonal transport in the cat's cervical sympathetic trunk (CST) on the superior cervical ganglion's choline acetyltransferase (ChAT) enzyme activity, acetylcholine (ACh) content, and ACh release. Electron microscopy on the segment of the CST exposed to colchicine 1 or 4 days earlier showed disappearance of microtubules and accumulation of vesicles and smooth membrane tubules but no disruption of the axonal cytomatrix. At 4 days following colchicine treatment, the number and size of synaptic boutons per grid square in the ganglion ipsilateral to the colchicine-treated CST were similar to those in the control ganglion. At 2 and 4 days following exposure of the CST to colchicine, ChAT activity in the ipsilateral ganglion was reduced to 78 +/- 8 and 54 +/- 8% of control values, respectively. ACh stores in the ganglia were also reduced (to 81 +/- 6% of control values at 2 days and to 51 +/- 5% of control values at 4 days). Ganglionic transmission and its sensitivity to blockade by hexamethonium during 2-Hz CST stimulation were not impaired at day 4 postcolchicine. ACh release evoked by 2-Hz stimulation of colchicine-treated axons was similar to release from untreated axons, despite the decrease in the ganglionic ACh content. In contrast, ACh release evoked by 20-Hz stimulation was depressed. The amount of ACh released during 5-Hz stimulation in the presence of vesamicol by the terminals of colchicine-treated axons was similar to that released by the terminals of untreated axons. These results suggest the following conclusions: (a) Colchicine-sensitive fast axonal transport contributes significantly to maintaining ChAT stores in preganglionic axon terminals. (b) The half-life of ChAT in sympathetic preganglionic terminals is approximately 4 days. (c) One consequence of colchicine-induced block of axonal transport is a reduced ACh content of preganglionic nerve terminals. (d) This decrease in ACh content appears to be the result of a loss in a reserve transmitter pool, whereas the size of the readily releasable compartment is maintained.
Tandon
A
A
Department of Pharmacology, McGill University, Montreal, Quebec, Canada.
Bachoo
M
M
Weldon
P
P
Polosa
C
C
Collier
B
B
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D002415:Cats; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003078:Colchicine / Q000494:pharmacology*; D005260:Female; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009333:Neck; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000648:ultrastructure; D013569:Synapses / Q000187:drug effects / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects
D002795:Choline O-Acetyltransferase; D000109:Acetylcholine; D003078:Colchicine