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H Thoenen

Publications and source records attributed to H Thoenen.

At least 235 records · Page 13Linked to original sources
PubMed1976

Lack of correlation between changes in cyclic nucleotides and subsequent induction of tyrosine hydroxylase in rat adrenal medulla.

Pretreatment of rats with dexamethasone (2.5 mumol/kg, a dose which blocks the release of ACTH from the pituitary gland) abolished the reserpine mediated increase in cAMP and the increase in the cAMP/cGMP ratio in the adrenal medulla. In contrast, the reserpine-mediated induction of tyrosine hydroxylase (TH) remained unchanged. Hypophysectomy had a similar effect to dexamethasone treatment. Since changes in cAMP and changes in the cAMP/cGMP ratio are not indispensible prerequisities for the subsequent induction of TH, a causal relationship between the two phenomena seems to be excluded.

Adrenal Medulla↗
PubMed1976

Synthesis, subcellular distribution and turnover of dopamine beta-hydroxylase in organ cultures of sympathetic ganglia and adrenal medullae.

The synthesis, subcellular distribution and turnover of dopamine beta-hydroxylase was studied in organ cultures of rat adrenal medullae and superior cervical ganglia. After exposure to [3H]leucine for 1 or 3 h, the tissues were homogenized at various time intervals and the amount of labelled dopamine beta-hydroxylase in different subcellular fractions (cytosol, soluble and membrane-bound fraction of catecholamine storage vesicles) was determined by immunoprecipitation and subsequent electrophoresis. In cultured adrenal medullae, induction of dopamine beta-hydroxylase initiated in vivo by administration of reserpine affected both soluble and membrane-bound pools of dopamine beta-hydroxylase to a similar extent after pulse-labelling for 1 or 3 h. The half-lives of dopamine beta-hydroxylase, which amounted to 6 h for the cytosol, 7.5 h for the soluble vesicular and 32 h for the membrane-bound vesicular pools were not altered by pretreatment with reserpine. In superior cervical ganglia the half-lives of the soluble pools were 2-3 times longer than in the adrenal medulla, whereas the half-life of the membrane-bound fraction was the same as in the adrenal medulla. In both organs the most heavily labelled fraction (both after a pulse of 1 or 3 h) was always that of the vesicular membrane, suggesting that newly-synthesized dopamine beta-hydroxylase is immediately incorporated into the storage vesicles and not via release into the cytosol from the site of synthesis. The fact that the half-life of membrane-bound dopamine beta-hydroxylase is markedly longer than that of the two soluble pools suggests that the single pools are not only independently supplied by newly-synthesized DBH but there is also no appreciable subsequent exchange between soluble and membrane-bound pools.

Adrenal Medulla↗
PubMed1975

Comparison between the retrograde axonal transport of nerve growth factor and tetanus toxin in motor, sensory and adrenergic neurons.

In previous studies it has been shown that nerve growth factor (NGF) is taken up with high selectivity by adrenergic and sensory nerve terminals and is transported retrogradely to the corresponding cell bodies by a colchicine sensitive mechanism 10,11,23. The present study was designed to investigate whether this retrograde transport of NGF depends on properties of the nerve terminals which are common to all the neurons or restricted to those which respond to NGF either during the whole life cycle (adrenergic neurons) or during a restricted period of embryonic development (sensory neurons). In order to investigate the retrograde transport of NGF in motor neurons we injected [125I]NGF into the musculus deltoideus and measured the side differences of accumulation of radioactivity in the spinal cord (C6-C8) from 4-48 h. At no time was there a preferential accumulation of radioactivity on the injected side. In contrast, tetanus toxin was accumulated preferentially on the injected side and an approximate rate of transport of 7.5 mm/h was calculated. Astonishingly there was also a retrograde transport of tetanus toxin in sensory and adrenergic neurons. The rate of transport was identical to that of NGF and the transport could be blocked by transection of the corresponding nerve fibers and local administration of colchicine. After unilateral injection of [125I]tetanus toxin into the forepaw or the musculus deltoideus light microscopic autoradiographs revealed heavily labeled neuronal cell bodies in the dorsal root ganglia or the ventrolateral spinal cord of the injected side. It is concluded that the retrograde transport of [125I]NGF depends on properties of the neuronal membrane which are specific for adrenergic and sensory neurons, whereas that of tetanus toxin is determined by features which are common to all, or at least to all peripheral, neurons. The fact that the rate of transport for both NGF and tetanus toxin is identical in all examined neurons, supports the hypothesis that the specificity of retrograde transport is determined by specific uptake sites in the neuronal membrane whereas the retrograde transport system is non-specific.

Animals↗
PubMed1975

Early effects of nerve growth factor on adrenergic neurons: an electron microscopic morphometric study of the rat superior cervical ganglion.

Nerve cells of the superior cervical ganglion of young rats (20 g body weight) were investigated electron microscopically 6 h, 24 h, 48 h and 5 days after subcutaneous injection of nerve growth factor (10 mug/g body weight every 24 h). By means of a planimetric method with high accuracy significant changes of the Nissl substance and the Golgi apparatus could be demonstrated as early as 6 h after injection. Within the Nissl bodies both the density of bound ribosomes on the cisternae of the rough endoplasmic reticulum and the density of free ribosomes and polysomes decreased in a given field. This finding reflects a rearrangement of the Nissl substance and a spreading over larger areas of the cytoplasm, indicating an activation of the ribosomal system. The Golgi apparatus, in particular its outer part, increases in volume with time of nerve growth factor treatment. On the other hand, the total cell volume does not show significant changes before 48 h of nerve growth factor treatment. At this time an increase in the cytoplasmic volume can be seen, whereas the nuclear volume remains unchanged. The possibility of correlations of the present findings with data from biochemical studies done under similar experimental conditions is discussed.

Animals↗
PubMed1975

Specificity of retrograde transport of nerve growth factor (NGF) in sensory neurons: a biochemical and morphological study.

In previous studies it has been shown that nerve growth factor (NGF) is taken up with a high selectivity by adrenergic nerve terminals and is transported retrogradely to the perikaryon11,22. It was the aim of the present experiments to investigate whether the sensory neurons exhibit the same high degree of selectivity for retrograde transport throughout the whole life cycle, although it is known that their dramatic response to NGF is confined to a short period of ontogenetic development. Unilateral injection of [125I]NGF into the forepaw of adult rats was followed by a preferential accumulation of radioactivity in the sensory ganglia (C6-C7) of the injected side. However, this preferential accumulation was not detectable earlier than 6 h after injection and reached a maximum (ratio between injected and non-injected side, 5:1) after 11-16 h. Transection of the plexus brachialis abolished and local administration of colchicine prior to that of [125I]NGF greatly reduced the preferential accumulation of radioactivity in the ganglia of the injected side. The rate of retrograde transport of NGF in sensory neurons was calculated to be 13 mm/h which is about 5 times faster than that in adrenergic neurons. The selectivity of this retrograde transport was demonstrated by the fact that injection of 125I-labeled bovine serum albumin and cytochrome c did not result in a preferential accumulation of radioactivity in the sensory ganglia of the injected side. Light microscopic autoradiography revealed heavily labeled cells in the sensory ganglia (C6-C7) of the injected side after administration of [125I]NGF into the forepaw. Only cells belonging to the large cell type were labeled. Prolonged (7 mug/g/day over 5 days) injection of NGF into the forepaw of 10-day-old rats did not result in a hypertropic response of the sensory neurons as far as can be judged from morphometric studies at the light microscopic level.

Age Factors↗
PubMed1975

Biological importance of retrograde axonal transport of nerve growth factor in adrenergic neurons.

Previous studies have shown that nerve growth factor (NGF) produces a selective induction of tyrosine hydroxylase (TH) in peripheral adrenergic neurons and that NGF is transported retrogradely with a high selectivity from the adrenergic nerve terminals to the perikaryon. In order to investigate the biological importance of retrograde NGF transport, the following experiments have been performed; (a) effect of NGF on TH activity in superior cervical ganglia (SCG) after unilateral injection into the anterior eye chamber and the submaxillary gland; and (b) effect of systemic injection of NGF on TH activity in SCG after blockage of retrograde axonal transport by axotomy. After unilateral injection of NGF into the anterior eye chamber and submaxillary gland of both 8-10-day-old rats and adult mice, the increase in TH activity in the SCG was considerably larger on the injected than on the non-injected side although the adrenergic neurons supplying the two organs do not account for more than 25% of the total number of adrenergic neurons in the SCG. A direct diffusion mechanism could be excluded by the fact that unilateral local injection of [125 I] produced no significant side difference in the accumulation of radioactivity in the SCG 2 after injection whereas after 14 h there was a several-fold difference between the injected and non-injected side. Moreover, the nodose ganglia which are located very close to the SCG exhibited no statistically significant difference in the accumulation of radioactivity at any time. Forty-eight hours after subcutaneous injections of 10 mg/kg of NGF the increase in TH activity of the SCG amounted to 154% on the intact side and to 92% on the axotomized side. However, these experiments do not permit decisions about the extent the axotomy, as such, impaired the response to NGF. It is concluded that the biological effect of NGF results to a considerable extent, from the moiety which reaches the cell body by retrograde transport from the nerve terminals.

Animals↗
PubMed1975

Effect of hypophysectomy on cAMP changes in rat adrenal medulla evoked by catecholamines and carbamylcholine.

It was the aim of this study to investigate the mechanisms responsible for changes in 3',5'-cyclic adenosine monophosphate (cAMP) in the rat adrenal medulla occuring after administration of carbamylcholine, histamine, ACTH and various phenylethylamines. Carbamylcholine, ACTH, histamine, noradrenaline and dopamine produced marked (500-900%) increases in adrenal cAMP which were very similar in both adrenal cortex and medulla both with respect to time-course and relative extent. Interestingly isoprenaline and adrenaline did not influence cAMP levels even at excessively high doses. In all cases studied transsection of the splanchnic fibers supplying the adrenals reduced the increase in medullary cAMP by not more than 25--30%, suggesting that cAMP levels in the adrenal medulla are predominantly regulated by non-neuronal mechanisms. This assumption was strongly supported by the observation that hypophysectomy completely abolished the 500--600% increase in cAMP produced by 50 mumol/kg of dopamine and reduced the 700% increase resulting from 4.4 mumol/kg of carbamylcholine to 70%. In spite of the marked increase in cAMP produced by single and repeated doses of dopamine in the adrenal medulla there was no subsequent induction of tyrosine hydroxylase (TH). Moreover carbamylcholine (8.2 mumol/kg) evoked TH induction only in innervated adrenals whereas after denervation, in spite of the large (+ 500%) and prolonged (more than 90 min) increase in cAMP, no TH induction could be observed. It is concluded that adrenal medullary cAMP is predominantly regulated by the pituitary gland via the adrenal cortex and only to a much smaller extent--if at all--by direct cholinergic mechanisms, which are responsible for the initiation of TH induction.

Adrenal Cortex↗
PubMed1975

Nerve growth factor induces volume increase and enhances tyrosine hydroxylase synthesis in chemically axotomized sympathetic ganglia of newborn rats.

Concomitant daily treatment of newborn rats for a 2-week to 1-month period with 10 mug/g of body weight of nerve growth factor and 100 mug/g of body weight of 6-hydroxydopamine produces in the cell bodies of adrenergic neurons the characteristic effects of the growth factor but in the nerve terminals the characteristic effects of 6-hydroxydopamine. The dual opposite effects result in a striking volume increase of sympathetic ganglia which far exceeds that produced by nerve growth factor alone. The selective induction of tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] in these chemically axotomized adrenergic neurons is even more pronounced than that produced by nerve growth factor alone in intact neurons.

Animals↗
PubMed1975

Circadian rhythm of tyrosine hydroxylase induction by short-term cold stress: modulatory action of glucocorticoids in newborn and adult rats.

The trans-synaptic induction of tyrosine hydroxylase [tyrosine 3-monooxygenase; EC 1.14.16.2, L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating)] in adrenal medulla and sympathetic ganglia by short-term (1-2 hr) cold stress (4 degrees) exhibits a circadian rhythm which seems to be causally related to the diurnal changes in adrenal glucocorticoid synthesis. In induction is maximal during the morning hours, when plasma corticoid concentrations (reflecting corticoid synthesis in the adrenal cortex) are minimal. In contrast, initiation of tyrosine hydroxylase induction in sympathetic ganglia is only possible in the afternoon. These observations suggest that tyrosine hydroxylase inducibility in the adrenal medulla is optimal during periods of low corticoid synthesis (the adrenal medulla is exposed to excessively high corticoid concentrations directly originating from the adjacent cortex), whereas in sympathetic ganglia an induction is only possible during the period of high plasma corticoid concentrations. This assumption is supported by the observation that in the first postnatal weeks, when the pituitary--adrenocortical system is not yet operating and plasma corticoid concentrations are low, initiation of tyrosine hydroxylase induction in the adrenal medulla is possible at any time of the day, whereas in sympathetic ganglia it is not possible at all. However, after administration of glycocorticoids initiation of tyrosine hydroxylase induction by short-term cold stress is also possible in newborn animals and in adults during the morning hours. The importance of glucocorticoids as modulators for the initiation of trans-synaptic tyrosine hydroxylase induction can also be deduced from the observation that in sympathetic ganglia kept in organ cultures and induction of the hydroxylase by cholinomimetics is only possible when glycocorticoids are added to the culture medium.

Adrenal Medulla↗