Neonatal capsaicin and guanethidine and axonally transported organelle-specific enzymes in sciatic nerve and in sympathetic and dorsal root ganglia

Abstract

The sciatic nerves of rats were 'dissected' by neonatal deletion of different types of neurons using relatively specific neurotoxins. The amounts of various enzyme activities in transit in different axonal types can be inferred by comparison of treated and control nerves. Accumulations by axoplasmic transport of selected enzyme activities proximal and distal to a tie placed on the sciatic nerve were monitored in adult rats exposed on the 2nd postnatal day to capsaicin (50 mg/kg) and/or to guanethidine (50 mg/kg daily, 5 days per week, from the 7th to the 28th postnatal day). Littermates were treated with the two vehicles. Proximal and distal accumulations of F--inhibitable acid phosphatase activity were reduced about 55% in animals pretreated with capsaicin and 10 to 20% in animals pretreated with guanethidine. The F--inhibitable acid phosphatase activity has been found to be the product of at least two different enzyme activities, one of which is relatively sensitive to L-(+)-tartrate inhibition, probably the lysosomal enzyme, and one rather resistant to tartrate inhibition. Accumulation of the tartrate-sensitive activity was reduced about 40% in the nerves of capsaicin-treated animals but was unaffected by guanethidine pretreatment. Accumulation of the tartrate-resistant activity was reduced about 70% in nerves of capsaicin-treated animals but was not significantly reduced in guanethidine-treated animals. Accumulation of acetylcholinesterase activity was reduced 35% by guanethidine pretreatment but was unaffected by capsaicin. Accumulations of the mitochondrial enzyme activities, glutaminase, hexokinase, and glutamic dehydrogenase, were reduced about 1/3 each by capsaicin and guanethidine pretreatment. The mitochondrial results were most clear-cut with glutaminase, which appeared to be relatively more active in axonal than in Schwann cell mitochondria. Transport of 125I-labeled nerve growth factor from the forepaw to the cervical dorsal root ganglia was reduced about 15% by capsaicin treatment. The concentrations of F--inhibitable acid phosphatase, β-glucuronidase, and glutaminase activities were reduced 20 to 30% in lumbar dorsal root ganglia of capsaicin-treated animals. Tartrate-sensitive acid phosphatase activity was reduced only 13%, while the tartrate-resistant activity fell 53%. Hexokinase and glutamic dehydrogenase activities were unchanged. Guanethidine had no effect upon enzyme activities measured in dorsal root ganglia. Tyrosine hydroxylase, acetylcholinesterase, glutaminase, and F--inhibitable acid phosphatase activities were reduced 86 to 98% in superior cervical ganglia from guanethidine-treated rats but were unaffected by capsaicin treatment. The results were interpreted to suggest that tartrate-inhibitable acid phosphatase activity, and perhaps lysosomes, are concentrated in the axons of the neurons which are susceptible to neonatal capsaicin, perhaps in response to a need for repeated repair of the peripheral terminals of these axons, whose function exposes them to increased risk of injury. Furthermore, unmyelinated axons, both sensory and sympathetic, appear to transport disporportionately large amounts of mitochondria, which may be a consequence of their high surface-to-volume ratio. In fixed tissue section,s there is an acid phosphatase activity found in the capsaicin-sensitive neurons of the dorsal root ganglia and in their terminals in the substantia gelatinosa. It seems likely that the tartrate-resistant acid phosphatase activity will prove to be this activity.