Abstract
In 134 male Wistar rats weighing 250–350g, the spinal cord was transected between the fifth and sixth thoracic vertebra. In the spinal cord above the lesion, concentrations of norepinephrine and serotonin increased three and twofold, respectively, compared with control levels. Below the lesion, however, the levels of these amines decreased significantly, and, after seven to twelve days, their concentrations were undetectable. In the brain stem, starting at seven days after transection, norepinephrine, serotonin, and histamine concentrations were sharply higher than those of controls. In the brain, during the first 24 hours, there were sharp fluctuations in serotonin, norepinephrine, and histamine concentrations; after which time, serotonin and histamine reached the control levels. Norepinephrine levels, however, dropped sharply at seven days and returned to normal levels thereafter. In the heart, the concentrations of serotonin dropped significantly to less than 40%, and those of norepinephrine and histamine dropped to less than 70% of the control. In the brain stem and adrenals, tyrosine hydroxylase activity reached a peak (two and fourfold increase, respectively) five days after spinal cord transection. The activity in the brain, however, reached a maximum (twofold above control) seven days after transection. Adrenal enzyme activity was still twice that of control, seven to thirty days after transection. In the spinal cord, changes in the enzyme activity were negligible at all times. Fluctuations in cyclic adenosine 3′, 5′-monophosphate levels were similar to those of tyrosine hydroxylase activity except that in the adrenals, there was a tenfold increase in its concentration five minutes following spinal cord transection.
The increase in tyrosine hydroxylase activity in the brain and brain stem may be partly due to curtailed end-product feedback inhibition and partly to reduced receptor activation. The sustained induction of the adrenal medullary tyrosine hydroxylase is probably a consequence of a continual stimulation of splanchnic nerve, resulting in de novo enzyme synthesis as indicated by the marked increase in c-AMP concentrations in the adrenals.
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References
Alousi, A., and Weiner, N. The regulation of norepinephrine synthesis in sympathetic nerves. Effect of nerve stimulation, cocaine and calcium releasing agents. Nat. Acad. Sci. 56: 1491–1496 (1966).
Anden, N.E., Haggendal, J., Magnusson, T., and Rosengrin, E. The time course of disappearance of norepinephrine and 5-hydroxytryptamine in the spinal cord after transection. Acta. Physiol. Scand. 62: 115–118 (1964).
Baumgarten, H.G., Bjorklund, A., Lachenmayer, L., Nobin, A., and Stenevi, U. Long-lasting selective depletion of brain serotonin by 5,6-dihydroxytryptamine. Acta. Physiol. Scand. (Suppl.) 373: 1–15 (1971).
Brostom, C.O., and Kon, C. An improved protein binding assay for cyclic-AMP. Analytical Biochem. 58: 459–468 (1974).
Carlsson, A., Kehr, W., Lindqvist, M., Magnusson, T., and Atack, C.V. Regulation of monoamine metabolism in the central nervous system. Pharmac. Rev. 24: 371–383 (1972).
Carlsson, A., and Lindqvist, M. Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta. Pharmak. Toxicol. 20: 140–144 (1963).
Carlsson, A., Falck, B., Fuxe, K., Hillarp, N.A. Cellular localization of monoamines in the spinal cord. Acta. Physiol. Scand. 60: 112–119 (1964).
Carlsson, A., Lindqvist, M., Magnusson, T., and Atack, C.V. Effect of acute transection on the synthesis and turnover of 5-HT in the rat spinal cord. Nauyn-Schmiedeberg’s Arch. Pharmacol. 277: 1–12 (1973)
Costa, E., Guidotti, A., and Hanbauer, I. Do cyclic nucleotides promote trans-synaptic induction of tyrosine hydroxylase? Life Sciences 14: 1169–1188 (1974).
Dahlstrom, A. Axoplasmic transport (with particular respect to adrenergic neurons). Phil. Trans. Roy. Soc. Lond. B. 261: 325–358 (1971).
Dairman, W., Gordon, R., Spector, S., Sjoerdsma, A., and Udenfriend, S. Increased synthesis of catecholamines in the intact rat following administration of β-adrenergic blocking agents. Mol. Pharmac. 4: 457–464 (1968).
Dontas, A.S., and Nickerson, M. Central and peripheral components of the action of “ganglionic” blocking agents. J. Pharmac. Exp. Ther. 12: 147–159 (1957).
Doppman, J.L., Zivin, J.A. A rapid non-operative technique for producing spinal cord injury in animals. Inves. Radiol. 11: 150–151 (1976).
Gilman, A.G. A protein binding assay for adenosine 3′5′-cyclic monophosphate. Proc. Nat. Acad. Sci. 67: 305–312 (1970).
Gordon, R., Reid, J.V.O., Sjoerdsman, A., and Udenfriend, S. Increased synthesis of norepinephrine in rat heart on electrical stimulation of stellate ganglia. Mol. Pharmac. 2: 610–613 (1966).
Gordon, R., Spector, S., Sjoerdsma, A., and Udenfriend, S. Increased synthesis of norepinephrine and epinephrine in the intact rat during exercise and exposure to cold. J. Pharmac. Exp. Ther. 153: 440–447 (1966).
Have, B.D., Neumayer, R.J., and Franz, D.N. Opposite effects of L-dopa and 5 hydroxytryptamine on spinal sympathetic reflexes. Nature 239: 336–337 (1972).
Iggo, A., and Vogt, M. Pre-ganglionic sympathetic activity in normal and reserpine treated cats. J. Physiol. (Lond.) 150: 114–133 (1960).
Ideda, M., Fahien, L.A., and Undenfriend, S. A kinetic study of bovine adrenal tyrosine hydroxylase. J. Biol. Chem. 241: 4452–4456 (1966).
Ito, A., and Schanberg, S.M. Central nervous system mechanisms responsible for blood pressure elevation induced by p-chlorophenylalanine. J. Pharmac. Exp. Ther. 181: 65–74 (1972).
Jequier, F., Robinson, D.S., Lovenberg, W., and Sjoerdsma, A. Further studies on tryptophan hydroxylase in rat brain stem and beef pineal. Biochem. Pharmac. 18: 1071–1081 (1969).
Koe, B.K., and Weissman, A. p-Chlorophenylalanine: A specific depletor of brain serotonin. J. Pharmac. Exp. Ther. 154: 499–516 (1966).
Kurosawa, A., Guidotti, A., and Costs, E. Induction of tyrosine-3-monooxygenase in adrenal medulla: role of protein kinase activation and translocation. Science 193: 691–693 (1976).
Kvetnansky, R., Gewirtz, G.P., Weise, V.K., and Kopin, I.J. Effect of dibutyryl cyclic AMP on adrenal catecholamine synthesizing enzymes in repeated immobilized hypophysectomized rats. Endocrinology 89: 50–55 (1971).
Levitt, M., Spector, S., Sjoerdsma, A., and Udenfriend, S. Elucidation of the rate-limiting step in norepinephrine biosynthesis in the prefused guinea pig heart. J. Pharmac. Exp. Ther. 148: 1–8 (1965).
Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J. Protein measurement with the folin phenol reagent. J. Biol. Chem. 193: 265–274 (1951).
McKay, A.V.P., and Iversen, L.L. Increased tyrosine hydroxylase activity of sympathetic ganglia cultured in the presence of dibutyryl cyclic AMP. Brain Res. 48: 424–426 (1972).
Mueller, R.A., Theonen, H., and Axelrod, J. Compensatory increase in adrenal tyrosine hydroxylase activity after chemical sympathectomy Science 163: 468–469 (1969).
Mueller, R.A., Theonen, H., Axelrod, J. Increase in tyrosine hydroxylase activity after reserpine administration. J. Pharmac. Exp. Ther. 169: 74–79 (1969).
Musacchio, J.M., and Wurzburger, R. Aggregation of beef adrenal tyrosine hydroxylase. Fed. Proc. 28: 287.
Naftchi, N.E., Lowman, E.W., Sell, G.H., Rusk, H.A. Peripheral circulation and catecholamine metabolism in paraplegia and quadriplegia. Arch. Phys. Med. and Rehabil. 53: 357–362 (1972).
Naftchi, N.E., Wooten, G.F., Lowman, E.W., Axelrod, J. Increased serum dopamine-β-hydroxylase activity during neurogenic hypertension in quadriplegia. In Frontiers in Catecholamine Research. G. Britain, Pergamon Press, 1973, pp. 1143–1147.
Naftchi, N.E., Wooten, G.F., Lowman, E.W., Axelrod, J. Relationship between serum dopamine-3-hydroxylase activity, catecholamine metabolism, and hemodynamic change during paroxysmal hypertension in quadriplegia. Circ. Res. 35: 850–861 (1974).
Naftchi, N.E., Demeny, M., Lowman, E., Tuckman, J. Hypertensive crises in quadriplegic patients: changes in cardiac output, blood volume, serum dopamine-3-hydroxylase activity, and arterial prostaglandin PGE2- Circ. 57: 336–341 (1978).
Naftchi, N.E., Demeny, M., DeCrescito, V., Tomasula, J., Flamm, S., Campbell, J.B. Biogenic amine concentrations in traumatized spinal cords of cats: effect of drug therapy. J. Neurosurg. 40: 52–57 (1974).
Nagatsu, T., and Undenfriend, S. A rapid and simple radioassay for tyrosine hydroxylase activity. Analytical Biochem. 9: 122–126 (1964).
Osterholm, J.L., Mathews, G.J. Altered norepinephrine metabolism following experimental spinal cord injury. Part I: Relationship to hemorrhagic necrosis and post-wounding neurological deficits. J. Neurosurg. 36: 386–394 (1972).
Sato, T.L., Jequier, E., Lovenberg, W., and Sjoerdsma, A. Characterization of tryptophan hydroxylating enzyme from malignant mouse mast cell. Eur. J. Pharmacol. 1: 18–25 (1967).
Sedvall, C.C., and Kopin, I.J. Influence of sympathetic denervation and nerve impulse activity on tyrosine hydroxylase activity in the rat submaxillary gland. Biochem. Pharmac. 16: 39–46 (1967).
Theonen, H., Mueller, R.A., and Axelrod, J. Trans-synaptic induction of adrenal tyrosine hydroxylase. J. Pharmac. Exp. Ther. 169: 249–254 (1969).
Waymere, J.C., Weiner, N., and Prasad, K.N. Regulation of tyrosine hydroxylase activity in cultured mouse neuroblastoma cells: Elevation induced by analogues of adenosine 3′,5′-cyclic monophosphate. Proc. Nat. Acad. Sci. (Wash.) 69: 2241–2245 (1971).
Weiner, N. Factors regulating catecholamine biosynthesis in peripheral and central catecholaminergic neurons. In The Nervous System, Vol. 1, The Basic Neurosciences, Raven Press, New York, 1975, pp. 341–354.
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Naftchi, N.E., Kirschner, A.K., Demeny, M., Viau, A. (1982). Changes in the CNS Biogenic Amines and Tyrosine Hydroxylase Activity After Spinal Cord Transection in the Rat. In: Naftchi, N.E. (eds) Spinal Cord Injury. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-6305-7_5
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DOI: https://doi.org/10.1007/978-94-011-6305-7_5
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