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Biomedical subjects

U Otten

Publications and source records attributed to U Otten.

At least 127 records · Page 7Linked to original sources
PubMed1978

Nerve growth factor-mediated induction of tyrosine hydroxylase in rat superior cervical ganglia in vitro.

Exposure of rat sympathetic ganglia to 3 microgram/ml of 2.5 S nerve growth factor (NGF) resulted in a 100% increase in tyrosine hydroxylase activity within 48 h. Pulselabeling of proteins with [3H]leucine, followed by immunoprecipitation with antibodies to tyrosine hydorxylase and isolation of the precipitated enzyme by gel electrophoresis, demonstrated that the increase in tyrosine hydroxylase activity was due to enhanced de novo synthesis. The incorporation of [3H]leucine into tyrosine hydroxylase was increased by 150% compared to a 17% increase in total protein synthesis, which was not statistically significant. The fact that the half-life of pulse-labeled tyrosine hydroxylase was the same for NGF-treated and control organ cultures of superior cervical ganglia excludes the possibility that enhanced tyrosine hydroxylase labeling by NGF is due to decreased degradation. We conclude that, without modulatory factors which play a role in vivo, NGF can enhance the synthesis of tyrosine hydroxylase in sympathetic ganglia in vitro, provided organ culture conditions which permit optimal survival of adrenergic neurons are selected.

Animals↗
PubMed1978

Nerve growth factor-induced fiber outgrowth from isolated rat adrenal chromaffin cells: impairment by glucocorticoids.

Addition of nerve growth factor to cultures of dissociated rat adrenal medullary cells caused fiber outgrowth from chromaffin cells. These fibers exhibited all the characteristics of neurites, particularly the formation of typical growth cones exhibiting intense catecholamine-specific fluorescence. Because this nerve growth factor-mediated neurite outgrowth could be abolished by physiological concentrations of glucocorticoids, it is concluded that the high glucocorticoid concentrations normally present in the adrenal medulla prevent the fiber outgrowth from medullary chromaffin cells in vivo. In dissociated sympathetic neurons the same concentrations of glucocorticoids markedly reduce but do not completely abolish neuronal fiber outgrowth.

Adrenal Medulla↗
PubMed1977

Selective induction of tyrosine hydroxylase and dopamine beta-hydroxylase by nerve growth factor: comparison between adrenal medulla and sympathetic ganglia of adult and newborn rats.

Administration of NGF to newborn and adult rats elicits a selective increase in TH and DBH both in sympathetic ganglia and adrenal medulla. This effect does not depend on intact preganglionic cholinergic fibers. The augmented enzyme activity results from enhanced enzyme synthesis since it can be abolished by cycloheximide and NGF has been shown to enhance the incorporation of [3H]leucine into DBH molecules. The responsiveness of the adrenal medulla to NGF is also supported by light and electron microscopic autoradiograms which show that intravenously injected 125I-NGF is accumulated with high selectivity in adrenal chromaffin as compared to adjacent adrenal cortical cells. In spite of the many similarities between the response of the adrenergic neurons and adrenal chromaffin cells to NGF, there are also two distinct differences. (a) In newborn rats the ratio between the TH increase effected by a single and 10 subsequent daily injections of NGF is 1:2 in the adrenal medulla and 1:7 in the superior cervical ganglia. (b) If adrenal medullae are transferred to organ culture after intravenous injection of NGF, maximal TH response is initiated 60-90 min after NGF administration. In superior cervical ganglia only a half-maximal response is initiated at that time. After a stationary phase a second increase starts after about 6 h to reach the maximum after 12 h. The biphasic time course of the initiation of TH induction by NGF in sympathetic ganglia is in agreement with the time course of 125I-NGF accumulation after intravenous injection27 reflecting the moiety of NGF reaching the cell bodies of the adrenergic neurons directly by the blood stream (initial accumulation) and by retrograde axonal transport (second phase).

Adrenal Medulla↗
PubMed1976

Mechanisms of tyrosine hydroxylase and dopamine beta-hydroxylase induction in organ cultures of rat sympathetic ganglia by potassium depolarization and cholinomimetics.

It was the aim of the present study to elucidate the mechanisms involved in specific tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) induction by potassium depolarization and cholinomimetics in rat superior cervical ganglia kept in organ culture. The effect of high (54 mM) potassium concentration on intact ganglia seems to result in a dual action: a) a specific induction of TH and DBH via release of acetylcholine from preganglionic cholinergic nerve terminals. b) a non-specific effect on terminal adrenergic neurons resulting in a general increase of protein synthesis as indicated by the increase in DOPA decarboxylase (DDC) and monoamine oxidase (MAO) activities. In decentralized superior cervical ganglia potassium depolarization failed to produce the specific TH and DBH induction although a small increase in DDC activity persisted. Carbamylcholine, acetylcholine and nicotine at concentrations of 10(-4) M elicited a selective induction of TH and DBH both in intact and decentralized ganglia via nicotinic receptor stimulation. Bethanechol, predominantly stimulating muscarinic receptors had no significant effect on TH activity. A 4 h pulse of 10(-4) M carbamylcholine produced optimal induction of DBH and TH 24 h and 48 h later respectively. Longer exposure to carbamylcholine resulted in a significantly smaller rise in TH activity.

Acetylcholine↗
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↗