To examine the biochemical events associated with the retrograde reaction in central noradrenergic neurons, changes in the activities of several enzymes subserving the metabolism of catecholamines, including tyrosine hydroxylase (TH),dopamine-beta-hydroxylase (DBH), DOPA decarboxylase (DDC), and monoamine oxidase (MAO), were measured in the nucleus locus coeruleus of rat brain following transection of the ascending axons from neurons in this nucleus by electrolytic lesions of the posterolateral hypothalamus. Such lesions produced a triphasic response in the activities of TH and DBH consisting of: (a) an increase to approximately 150 percent of control during the first 48 h followed by (b) a reduction reaching 60 percent of control by day 14, and (c) a full recovery of activity by day 21-28. In contrast, the activities of DDC and MAO, enzymes non-specific for catecholamine neurons, were unchanged. Immunochemical titration with specific antibodies to TH and DBH demonstrated that the fall in enzyme activity was entirely attributable to reduced accumulation of specific enzyme protein and not inhibition of pre-existing enzyme molecules. There was no reduction in the number of neurons in the nucleus locus coeruleus as a consequence of the lesion. We conclude that a reduction in the accumulation of specific enzymes subserving transmitter biosynthesis characterizes a reversible retrograde reaction of central noradrenergic neurons. The coincidence of the time course of reduced enzyme accumulation with regenerative sprouting from damaged noradrenergic axons and also the absence of classical signs of chromatolysis in locus coeruleus neurons following comparable lesions suggest that, first, during the retrograde reaction there may be a reordering of priorities governing accumulation of specific proteins favoring accumulation of those required for reconstitution of cellular processes by sprouting at the expense of proteins utilized in the synthesis of neurotransmitters, and second, some intrinsic neurons of the CNS may undergo reversible biochemical changes of a retrograde reaction in the absence of the classical morphological appearance of chromatolysis.

Animals↗

PubMed1975

The effects of the catecholamines and related drugs on intraocular pressure.

This review offers a short summary of present knowledge of the physiology and pharmacology of the sympathetic system with particular reference to its role in the control of intra-ocular pressure. The ocular effects of epinephrine and some related amines are discussed as as new and interesting developments which promise significant increase in the efficiency of drugs in the treatment of glaucoma.

Aqueous Humor↗

PubMed1975

Effects of reserpine on activities and amounts of tyrosine hydroxylase and dopamine-beta-hydroxylase in catecholamine neuronal systems in rat brain.

Reserpine (10 mg/kp i.p.) increased the activities of the enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase, but not dopa decarboxylase, 2- to 3-fold in the nucleus locus ceruleus of rat brain. The TH response was dose-dependent, reached a maximum by 48 hours and recovered by 3 weeks. The increased activities of TH and dopamine-beta-hydroylase were shown by immunotitration with specific antibodies to each enzyme to be due entirely to increased accumulation of specific enzyme protein. At a time when the reserpine-elicited accumulation of TH was increased 300% in the locus ceruleus, activity of the enzyme only increased 20% in hypothalamus and not at all in substantia nigra or caudate nucleus. Reserpine increased the accumulation of TH, primarily in the cell bodies and to a far less degree in the terminals of neurons of locus ceruleus but not in dopaminergic neurons of the nigrostriatal system. The time course of enzyme accumulation parallels that of depletion of monoamines in brain.

Animals↗

PubMed1974