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T P Rothman

Publications and source records attributed to T P Rothman.

39 records · Page 3Linked to original sources

Catecholamine biosynthetic enzymes are expressed in replicating cells of the peripheral but not the central nervous system.

We sought to determine whether the precursors of catecholamine-containing neurons in the developing peripheral and central nervous systems of chickens and rats express the biosynthetic enzymes tyrosine hydroxylase [THase; tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] or dopamine beta-hydroxylase [DBHase; 3,4-dihydroxyphenylethylamine, ascorbate:oxygen oxidoreductase (beta-hydroxylating), EC 1.14.17.1], prior to the time they withdraw from the cell cycle. Chicken embryos (stages 26-27) were injected with [3H-thymidine and 4 hr later were prepared for the simultaneous demonstration of radioautographically labeled nuclei in immunoreactive THase cells. The brains and sympathetic chains of rat fetuses (days E12-E14), exposed for 2 hr to [3H]thymidine, were treated similarly except that peripheral tissues were stained with a specific antibody to DBHase as well as anti-THase. In the peripheral nervous system of both chicken and rat, nuclei of THase-containing cells were radioautographically labeled. DBHase-containing cells in the peripheral nervous system of rats were also labeled and thus are noradrenergic. THase was localized in cells of the brain of the same rat fetuses beginning on day E12 (no THase was detected on day E11 or E11.5) in the mantle layer of the ventral mesencephalic and rostrolateral rhombocephalic cellular groups; however. THase-containing cells in the central nervous system did not incorporate [3H]thymidine. We conclude that, during development, the adrenergic neuronal precursors of the peripheral nervous system but not of the central, have the capacity to synthesize catecholamines before they withdraw from the cell cycle. Differences in the maturation of peripheral and central neurons may be related to differences in their embryological origin.

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Separately developing axonal uptake of 5-hydroxytryptamine and norepinephrine in the fetal ileum of the rabbit.

Uptake of 5-hydroxytryptamine (5-HT) by adult and fetal rabbit's ileum was studied. The adult myenteric plexus accumulated tritium when incubated with tritiated 5-HT. However, in addition to labeled 5-HT, tritiated 5-hydroxyindole acetic acid and, when monoamine oxidase (MAO) was inhibited, 5-HT-o-glucuronide were found in the tissue. Two uptake processes differing in affinity could be defined. Only the high affinity process was saturable. Fetal ileum took up tritiated 5-HT but glucuronidation did not occur when MAO was inhibited. The uptake of tritiated 5-HT by the fetal ileum was due to a single, saturable, temperature sensitive (Q10 at 27-37 degress C = 2.4) process inhibited by ouabain. It was identical to the high affinity uptake found in adult tissue. This specific high affinity uptake could be found as early as the 16th day of gestation, 5-8 days before uptake of norepinephrine (NE) begins. Light and electron microscope radioautography revealed that the uptake of 5-HT was primarily into axons and a characteristic structure called the expanded process, both in the myenteric plexus. Both contained dense-cored vesicles. Axons were not labeled by tritiated NE until after 24 days and the expanded process was never labeled by tritiated NE. This study shows that uptake of 5-HT is a property of distinct system of axons in the mammalian myenteric plexus which develops prior to adrenergic axons during ontogeny.

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