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Biomedical subjects

U Otten

Publications and source records attributed to U Otten.

At least 109 records · Page 6Linked to original sources
PubMed1982

Nerve growth factor increases substance P, cholecystokinin and vasoactive intestinal polypeptide immunoreactivities in primary sensory neurones of newborn rats.

Immunoreactive substance P, somatostatin, gastrin/cholecystokinin and vasoactive intestinal polypeptide were studied in lumbar dorsal root ganglia of 14-day-old rats treated from day 2 to 11 of life with nerve growth factor. Increased staining intensity of neuronal cell bodies and processes for substance P, gastrin/cholecystokinin and vasoactive intestinal polypeptide was observed by immunohistochemistry indicating increased neuronal peptide concentrations. These results were supported by radioimmunoassays showing increased ganglionic levels of substance P and vasoactive intestinal polypeptide. Both techniques, however, failed to show a significant increase of somatostatin levels.

Animals↗
PubMed1982

Correlation between substance P content of primary sensory neurones and pain sensitivity in rats exposed to antibodies to nerve growth factor.

An experimental autoimmune model was used to study effects of nerve growth factor deprivation on the peptide content of sensory neurones and on pain sensitivity. Rats exposed during development to anti-nerve growth factor antibodies showed an increased threshold towards nociceptive stimuli. These animals also showed a significant decrease in substance P levels in their dorsal root ganglia and spinal cord. These results suggest that substance P-containing primary sensory neurones are involved in certain types of nociception.

Animals↗
PubMed1982

Effects of antibodies against nerve growth factor on the postnatal development of substance P-containing sensory neurons.

Administration of anti-nerve growth factor (NGF)-antibodies to newborn rats produces a marked but reversible reduction of the substance P content in dorsal root ganglia. This is in contrast to the effect of anti-NGF-antibodies on sympathetic ganglia, where they cause a destruction of the adrenergic neurons as is evident in the irreversible reduction of tyrosine hydroxylase activity.

Animals↗
PubMed1981

Stimulation of the pituitary-adrenocortical axis and induction of tyrosine hydroxylase by nerve growth factor are not dependent on mouse submaxillary gland isorenin.

A biologically active 2.5S NGF preparation free of renin-activity was prepared. Stimulation of the hypothalamo-pituitary-adrenocortical axis as well as induction of tyrosine hydroxylase in sympathetic ganglia are characteristic NGF effects and are not mediated by renin. These findings are confirmed by observations showing that captopril, an angiotensin converting enzyme inhibitor, failed to block these responses.

Adrenocorticotropic Hormone↗
PubMed1981

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

Nerve growth factor is retrogradely transported in sympathetic and sensory neurons throughout life. Although this transport is known to be biologically significant in sympathetic neurons, such a function was not yet known in sensory ganglia. By using the neuropeptide substance P as a biochemical marker, we show that sensory ganglia from newborn and adult rats respond in nerve growth factor and that its retrograde axonal transport is biologically relevant, as indicated by an increase in substance P and in general protein content.

Animals↗
PubMed1981

Shape changes induced by biologically active peptides and nerve growth factor in blood platelets of rabbits.

1 Nerve growth factor (NGF), substance P (SP) and thymopoietin all caused shape change reactions of rapid onset in rabbit platelets. NGF had the highest maximal effect, and SP the lowest EC50 (concentration causing half maximal shape change). The action of SP was reversible within 5 min, whereas that of NGF lasted for at least 1 h. A series of other peptides were inactive. 2 After preincubation of platelets with SP, a second application of SP no longer caused a shape change reaction, whereas the effect of NGF was not influenced. 3 An oxidized NGF-derivative without biological activity did not cause a shape change reaction, neither did epidermal growth factor. 4 Prostaglandin E1 (PGE1) and pretreatment of the platelets with 3% butanol, which counteract the shape changes caused by 5-hydroxytryptamine (5-HT) and adenosine 3',5'-diphosphate, also antagonized those induced by NGF and SP. Neither heparin nor methysergide, an antagonist of 5-HT-receptors, influenced the shape change induced by NGF or SP. The action of NGF was also antagonized by a specific antibody to NGF. 5 Thymopoietin, like the basic polypeptide polyornithine (mol. wt. 40,000) was not antagonized by PGE1 and butanol. Heparin, which counteracted the effect of polyornithine, did not influence that of thymopoietin. 6 In conclusion, different modes of action are involved in the shape change of blood platelets induced by polypeptides and proteins. SP and NGF may act by stimulating specific membrane receptors.

Animals↗
PubMed1980

Immunosympathectomy: lack of evidence for a complement-mediated cytotoxic mechanism.

To determine whether the destruction of peripheral sympathetic neurons by anti-NGF-antibodies results from a complement-mediated cytotoxic action or from the deprivation of endogenous NGF or immunologically NGF-like cross-reacting molecules we investigated the time-course of the reversibility of the effect of NGF-antibodies by neutralizing doses of NGF, together with the effect of NGF-antibodies in complement-deficient mice. After administration of a single dose of 50 mg/kg of purified antibodies to newborn rats the TH level was reduced to 75% of controls after 12 h, to 48% after 24 h, 39% after 36, and 28% after 48 h. After this time no further reduction occurred and levels remained constant up to 14 days. The effect of the NGF-antibodies was reversible on addition of NGF up to 48 h after antibody administration. Although the reversibility was not complete (85% of controls) the extent of the reversibility was the same whether NGF was given 12 or 48 h after the antibodies. The incompleteness of the reversibility is reflected by the small number of degenerating neurons apparent as early as 12 h after antibody administration. Since these early degenerative effects were also seen in complement-deficient mice it is concluded that they involve a small population of neurons, sensitive to short-term NGF deprivation whereas the majority of the neurons can withstand deprivation for up to 48 h without sustaining irreversible damage.

Adrenergic Fibers↗
PubMed1980

Requirement of nerve growth factor for development of substance P-containing sensory neurones.

The protein nerve growth factor (NGF) is known to be essential for the maturation and maintenance of adrenergic neurones and for the development of sensory neurones during critical stages of embryonic life. The investigation of the physiological importance of NGF for the development of sensory neurones has been hampered so far by the lack of biochemical marker substances for these neurones. The demonstration that the undecapeptide substance P(SP) is present in sensory neurones suggests that it might be such a marker. SP is synthesized in dorsal root ganglia (DRG) and transported to the terminals of C-fibres located in the dorsal horn of the spinal cord and in the skin. Its release can be demonstrated from the central and peripheral endings of sensory nerve fibres which seem to have an important role in pain perception. We have investigated the effects of NGF and of purified anti-NGF antibodies on the content of SP in rat DRG and in their respective target organs, namely the spinal cord and the skin. The effects on sympathetic ganglia were included in order to control the effectiveness of both NGF and its antibody. We report here that NGF leads to an increase in SP in spinal ganglia, as previously shown by Kessler and Black. However, in contrast to these authors, we describe that the administration of anti-NGF antibodies produces a marked reduction of the SP content in sensory neurones and in their respective nerve terminals.

Animals↗
PubMed1980

Dopamine, norepinephrine and serotonin production by an intestinal carcinoid tumor.

Substantial amounts of both dopamine and norepinephrine in addition to serotonin were found in a mesenteric metastasis of an ileal carcinoid tumor. Correspondingly, the norepinephrine-synthesizing enzymes were present in the tumor tissue and tyrosine hydroxylase was found in amounts substantially higher than the levels normally present in adrenal medullary cells. These findings confirm that the carcinoid tumors belong to the APUDomas and indicate that catecholamines might play an important role in the pathogenesis of the carcinoid syndrome.

Apudoma↗
PubMed1980

The role of sodium influx mediated by nicotinic receptors as an initial event in trans-synaptic induction of tyrosine hydroxylase in adrenergic neurons.

1. Isolated superior cervical ganglia of the rat were incubated for 2--30 min (37 degrees C) in Krebs' solution or tissue culture medium (BGJb) containing 22Na and then washed for 30 min in ice-cold 22Na-free Krebs' solution (to clear extracellular space). The radioactivity remaining in the ganglia was taken as a measure of 22Na influx into the intracellular compartment of the ganglion. 2. Addition of cholinomimetics (100 microM nicotine or 100 microM carbachol) to the incubation led to an increase in 22Na influx. This increase reached maximal values after 10 min of incubation; it was more pronounced after incubation in Krebs' solution than in BGJb medium. 3. While chlorisondamine (3 microM) or dopamine (100 microM) greatly reduced the carbachol-induced 22Na influx, tetrodotoxin (2 microM) did not have any effect. 4. In ganglia obtained from animals treated with 6-hydroxydopamine in the early postnatal phase (resulting in an extensive destruction of peripheral sympathetic neurons) neither carbachol (100 microM) nor nicotine (100 microM) produced an increase in 22Na influx demonstrating that the intraneuronal compartment is responsible for this enhanced influx. 5. The effects of dopamine, chlorisondamine and tetrodotoxin on the carbachol-induced 22Na uptake into superior cervical ganglia are similar to their effects on carbachol-mediated induction of tyrosine hydroxylase in superior cervical ganglia kept in tissue culture (Thoenen and Otten 1977b). It is concluded that the induction of tyrosine hydroxylase via nicotinic receptors is closely linked to the enhanced sodium influx into the adrenergic neurons mediated by the same receptors.

Animals↗
PubMed1979

Stimulation of the pituitary-adrenocortical axis by nerve growth factor.

Nerve growth factor (NGF) is a protein essential for the development and maintenance of the peripheral sympathetic nervous system, causing responsive neurones to increase in size and to extend neurites. Biochemically, the selective induction of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase key enzymes in catecholamine biosynthesis is one of its most characteristic effects. Both the morphological and biochemical effects are modulated by glucocorticoids, suggesting a close relationship between specific effects of NGF and hormone action. NGF has been shown to induce an increase in adrenal cyclic AMP in intact but not in hypophysectomised rats, and so we have looked directly at the effect of systemic administration of NGF on the hypothalamo-pituitary-adrenal axis. We report here that NGF induced an enhanced secretion of adrenocorticotropin (ACTH) and a prolonged increase in plasma glucocorticoid concentration after intravenous (i.v.) injection. Such effects could have important implications for the biological activity of NGF.

Adrenocorticotropic Hormone↗
PubMed1979

Immunization of adult rats against 2.5 S NGF: effects on the peripheral sympathetic nervous system.

The biochemical and morphological changes effected by immunization of adult rats with 2.5 S mouse nerve growth factor (NGF) were studied in sympathetic ganglia and in representative target organs. This immunization procedure maintains high levels of circulating anti NGF-antibody for periods of months. Morphological analysis revealed a general reduction in the size of the adrenergic neurons in the superior cervical ganglion (SCG) which was also reflected at the biochemical level by a 30% decrease in total protein content and a 50--60% reduction in the total activities of all norepinephrine-synthesizing enzymes. However, there was no change in total choline acetyltransferase activity. The biochemical and morphological changes observed in the SCG seem to be confined to the neuronal cell body, since at any stage of immunization target organs (the submandibular and the pineal gland) remained unaffected. All sympathetic ganglia investigated--except the superior mesenteric ganglion--responded in a similar way to the immunization against 2.5 S NGF. These changes in the adrenergic cell bodies were largely reversible. The recovery of normal enzyme activities followed closely the decrease of the antibody titer after cessation of immunization boosting. This indicates that cell death is not caused by anti NGF-antibodies in ganglia of adult animals. Thus, in contrast to adrenergic neurons from newborn animals, which depend on NGF or a crossreacting NGF-like material for survival, differentiated adrenergic neurons need this factor for the maintenance of their normal function but not for survival.

Animals↗
PubMed1979

Nerve growth factor (NGF) in the rat CNS: absence of specific retrograde axonal transport and tyrosine hydroxylase induction in locus coeruleus and substantia nigra.

Selective, highly efficient uptake of [125I]NGF by nerve terminals followed by retrograde axonal transport, and specific induction of tyrosine hydroxylase by NGF are well known phenomena in peripheral adrenergic neurons of adult rats. In the present study these parameters were used in order to detect possible interactions of NGF with central catecholaminergic neurons. No selective retrograde transport of [125I]NGF could be detected by light microscopic autoradiography from the caudate nucleus to the dopaminergic neurons in the substantia nigra or from the hippocampus to the noradrenergic nerve cells of the locus coeruleus. Biochemically, no change in tyrosine hydroxylase activity could be observed for up to 3 days after injection of either NGF, anti-NGF antibodies, or control proteins close to the nerve cell bodies in the substantia nigra or the locus coeruleus. These data suggest a fundamental difference between central and peripheral adrenergic neurons with regard to their responsiveness of NGF.

Adrenergic Fibers↗