Synopsis
Guanethidine is known to cause a loss of catecholamines from sympathetically innervated tissues and sympathetic ganglia in adult animals but its effect on newborn animals has not been examined.
Newborn rats were injected daily with guanethidine (20 mg/kg body weight) for 8 days. They were killed when 1 month-old along with untreated litter mate controls. Catecholamines were demonstrated in the iris, in the pineal body and in sympathetic ganglia, using the formaldehyde-induced fluorescence method.
In the guanethidine-treated rats there was a complete loss of fluorescent nerve fibres from the pineal body and an almost complete loss of similar fibres from the iris. The sympathetic ganglia were reduced to less than 10% of the control ganglia, and the number of nerve cell bodies per unit area was decreased in the ganglion remnants.
It is concluded that guanethidine causes, in newborn rats, an irreversible destruction of most sympathetic neurons, i.e. a chemical sympathectomy closely resembling that obtainable in newborn animals by injections of 6-hydroxydopamine or antiserum to nerve growth factor.
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References
Angeletti, P. U. (1971). Chemical sympathectomy in newborn animals.Neuropharmacol. 10, 55–9.
Angeletti, P. U. &Levi-Montalcini, R. (1970a). Sympathetic nerve cell destruction in newborn mammals by 6-hydroxydopamine.Proc. Nat. Acad. Sci. 65, 114–21.
Angeletti, P. U. &Levi-Montalcini, R. (1970b). Cytolytic effect of 6-hydroxydopamine on neuroblastoma cells.Cancer Res. 30, 2863–9.
deChamplain, J., Malmfors, T., Olson, L. &Sachs, Ch. (1970). Ontogenesis of peripheral adrenergic neurons in the rat: pre- and postnatal observations.Acta physiol. scand. 80, 276–88.
Cohen, S. (1960). Purification of a nerve growth promoting protein from mouse salivary gland and its cytotoxic antiserum.Proc. Nat. Acad. Sci., Wash. 46, 302–11.
Eränkö, O. (1967). The practical histochemical demonstration of catecholamines by formaldehyde induced fluorescence.J. R. microsc. Soc. 87, 259–76.
Eränkö, O. &Eränkö, L. (1971a). Loss of histochemically demonstrable catecholamines and acetylcholinesterase from sympathetic nerve fibres of rat pineal after chemical sympathectomy with 6-hydroxydopamine.Histochem. J. 3, 357–63.
Eränkö, L. & Eränkö, O. (1971b). Effect of 6-hydroxydopamine on the ganglion cells and the small intensely fluorescent cells in the superior cervical ganglion of the rat.Acta physiol. scand. In press.
Furness, J. B., Campbell, G. R., Gillard, S. M., Malmfors, T., Cobb, I. L. S. &Burnstock, G. (1970). Cellular studies of sympathetic denervation produced by 6-hydroxydopamine in the vas deferens.J. Pharmacol. exp. Ther. 174, 111–22.
Jensen-Holm, J. &Juul, P. (1970). The effect of guanethidine, pre- and postganglionic nerve division on the rat superior cervical ganglion: Cholinesterases and catecholamines (histochemistry), and histology.Acta pharmacol. et toxicol. 28, 283–98.
Levi-Montalcini, R. &Angeletti, P. U. (1966). Immunosympathectomy.Pharmacol. Rev. 18, 619–28.
Machado, A. B. M. (1971). Electron microscopy of developing sympathetic fibres in the rat pineal body.Progr. Brain Res. 34, 171–86.
Malmfors, T. &Sachs, Ch. (1968). Histochemical studies on the accumulation of noradrenaline after depletion with guanethidine, metaraminol or an inhibitor of noradrenaline synthesis, H 44/68.Europ. J. Pharmacol. 2, 265–75.
Mitchell, J. R. &Oates, I. A. (1970). Guanethidine and related agents. I. Mechanism of the selective blockade of adrenergic neurons and its antagonism by drugs.J. Pharmacol. exp. Ther. 172, 100–7.
Porter, C. C., Totaro, J. A. &Stone, C. A. (1963). Effect of 6-hydroxydopamine and some other compounds on the concentration of norepinephrine in the hearts of mice.J. Pharmacol. exp. Ther. 140, 308–16.
Sanan, S. &Vogt, M. (1962). Effect of drugs on the noradrenaline content of brain and peripheral tissues and its significance.Brit. J. Pharmacol. 18, 109–27.
Saner, A. &Thoenen, H. (1971). Model experiments on the molecular mechanism of action of 6-hydroxydopamine.Molec. Pharmacol. 7, 147–54.
Stone, C. A., Porter, C. C., Stavroski, J. M., Ludden, C. T. &Totaro, J. A. (1964). Antagonisms of certain effects of catecholamine-depleting agents by antidepressants and related drugs.J. Pharmacol. exp. Ther. 144, 196–204.
Thoenen, H. (1969).Bildung und funktionelle Bedeutung adrenerger Ersatztransmitter. Berlin, Heidelberg & New York: Springer-Verlag.
Thoenen, H. &Tranzer, J. P. (1968). Chemcial sympathectomy by selective destruction of adrenergic nerve endings with 6-hydroxydopamine.Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 261, 271–88.
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Eränkö, O., Eränkö, L. Histochemical evidence of chemical sympathectomy by guanethidine in newborn rats. Histochem J 3, 451–456 (1971). https://doi.org/10.1007/BF01014783
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DOI: https://doi.org/10.1007/BF01014783