Inhibition of the retrograde axonal transport of dopamine-beta-hydroxylase antibodies by the calcium ionophore A23187.
High levels of calcium, as well as calcium ionophores, have been reported to inhibit the anterograde transport of proteins. The effect of the calcium ionophore, A23187, on the retrograde axonal transport of proteins was therefore investigated. The uptake of antibodies to dopamine-beta-hydroxylase (anti-D beta H) by sympathetic nerve terminals in the iris and their subsequent accumulation in the superior cervical ganglion was inhibited by up to 65% by A23187 (6 nmol, i.o.). At this dose, catecholamine fluorescence in the iris was reduced, indicating a high rate of exocytosis, but tyrosine hydroxylase levels and the capacity of the treated irides to take up noradrenaline were unaffected. Higher amounts of A23187 (28 nmol, i.o.) did not cause a greater degree of inhibition of retrograde transport. However, this dose was toxic to the neurons, as shown by a 68% decrease in the ability of the nerve terminals in the iris to take up [3H]noradrenaline. This loss of function occurred gradually over a 12-h period. On the other hand, tyrosine hydroxylase levels were unaffected by 28 nmol A23187. The toxicity of A23187 may be a consequence of a build up in intracellular calcium, but such toxicity did not lead to any apparent loss of nerve terminals within a 3-day period.
Lees
G J
GJ
D000818:Animals; D000906:Antibodies; D001370:Axonal Transport / Q000187:drug effects*; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D004299:Dopamine beta-Hydroxylase / Q000276:immunology* / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000378:metabolism; D007498:Iris / Q000294:innervation; D051379:Mice; D013564:Sympathetic Nervous System / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000906:Antibodies; D000001:Calcimycin; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D002118:Calcium