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Biomedical subjects

M Goedert

Publications and source records attributed to M Goedert.

At least 181 records · Page 10Linked to original sources
PubMed1985

Nerve growth factor counteracts the neurophysiological and neurochemical effects of chronic sciatic nerve section.

The sciatic nerve was sectioned unilaterally in rats and nerve growth factor (NGF) applied locally to the nerve stump for the following 10-14 days using an indwelling osmotic pump. The aim of the experiment was to test whether NGF had any effect on the previously reported neurophysiological and neurochemical events that occur central to a peripheral nerve lesion. The method of application allowed the sciatic nerve on the other side to be used as a control. Primary afferent depolarization fell, as expected, to 13% of its control value after chronic nerve section but if NGF was administered it fell to only 43.5% of control. Chronic nerve section is also known to result in expansion of the receptive fields of deafferented dorsal horn cells. NGF treatment reduced the number of such large receptive fields by 50%. The normal depletion of fluoride resistant acid phosphatase from the cut nerve terminals in the dorsal horn did not occur following NGF treatment. Radioimmunoassay of substance P revealed that the 30% reduction in dorsal horn levels that follows chronic sciatic nerve section did not occur when NGF was applied and that the accompanying 60% decrease in dorsal root ganglion levels was changed to a 64% increase by NGF. The results show that chronic NGF treatment of a cut sciatic nerve does partially reverse the central changes that normally follow deafferentation.

Acid Phosphatase↗
PubMed1985

Mammalian tachykinin-induced hydrolysis of inositol phospholipids in rat brain slices.

The mammalian tachykinins substance K, neuromedin K and substance P stimulated inositol phospholipid hydrolysis in paired coronal sections through the rat brain. In contrast, none of these peptides had any effect on either basal or forskolin-stimulated cyclic AMP levels. The present results therefore implicate inositol phospholipid hydrolysis as a possible second messenger system mediating the effects of substance K and neuromedin K in addition to substance P.

Animals↗
PubMed1985

The ontogenetic development of neurotensin-like immunoreactivity and neurotensin receptors in the cat striatum.

At birth, striatal neurotensin-like immunoreactivity amounted to 10% of the adult values which were reached at the age of 5 weeks. In the caudate nucleus neurotensin-like immunoreactivity presented a patchy distribution throughout development that was in register with Met-enkephalin staining, whereas [3H]neurotensin binding sites were most heavily concentrated in the background matrix. Thus, the adult distribution pattern of neurotensin-like immunoreactivity and [3H]neurotensin binding sites is already established at birth.

Animals↗
PubMed1984

Neurotensin stimulates inositol phospholipid hydrolysis in rat brain slices.

Neurotensin stimulated inositol phospholipid hydrolysis in matched coronal vibratome sections through the rat brain. This effect was tetrodotoxin-resistant and a good correlation was noticed between the magnitude of neurotensin-stimulated inositol phospholipid hydrolysis and the number of specific [3H]neurotensin binding sites in various brain regions. Neurotensin produced no significant effect on either basal or stimulated cAMP levels.

Animals↗
PubMed1984

The comparative distribution of xenopsin- and neurotensin-like immunoreactivity in Xenopus laevis and rat tissues.

The regional distribution of xenopsin-like immunoreactivity (XPLI) and of neurotensin-like immunoreactivity (NTLI) was studied by radioimmunoassay in tissues of Xenopus laevis and rat. In Xenopus laevis, XPLI showed a wide distribution throughout central and peripheral tissues with the highest concentration in the skin; NTLI was found in both central and peripheral tissues with the exception of the skin. Gel chromatography on Sephadex G-25 was used in order to characterize the immunoreactive material; both XPLI and NTLI eluted in a single peak at the position of synthetic xenopsin and neurotensin. No XPLI could be detected in central and peripheral tissues from mouse, rat, guinea-pig, rabbit or cat. In contrast, NTLI was found in a variety of peripheral tissues of the rat and it coeluted with synthetic neurotensin on reverse phase high-performance liquid chromatography. It is probably present in preganglionic parasympathetic nerve fibres.

Animals↗
PubMed1984

Specific binding of tritiated neurotensin to rat brain membranes: characterization and regional distribution.

The characteristics of [3H]neurotensin binding were studied using membranes prepared from the rat brain. Binding of [3H]neurotensin was found to be specific, saturable and reversible. Under the conditions of the assay non-specific binding represented less than 20% of the total binding at a radioligand concentration of 2 nM. The specific [3H]neurotensin binding increased linearly with protein concentration and was dependent on the pH and the temperature of the incubation medium. At 25 degrees C equilibrium was reached rapidly and the association kinetics appeared to be monophasic. The dissociation was not monophasic and it could be resolved into two distinct components. Scatchard analysis of the saturation data indicated a single population of binding sites with a density of 432 fmol/mg protein and an equilibrium dissociation constant of 2.85 nM. A Hill transformation of the competitive inhibition of specific [3H]neurotensin binding by increasing concentrations of unlabelled peptide yielded a slope not significantly different from unity. Neurotensin 1-13 and various neurotensin analogues were tested for their ability to compete with [3H]neurotensin for its binding site. Neurotensin 1-13, neurotensin 8-13 and the amphibian skin peptide xenopsin were equipotent and strongly inhibited the specific binding of [3H]neurotensin. Neurotensin 9-13 and the chicken intestinal peptide Lys8,Asn9-neurotensin 8-13 were weakly active, whereas neurotensin 10-13 and the amino-terminal fragments neurotensin 1-6, neurotensin 1-8 and neurotensin 1-11 were inactive. Physiological concentrations of sodium chloride inhibited specific [3H]neurotensin binding, whereas divalent cations and guanyl nucleotides did not produce a significant change in either the equilibrium dissociation constant or the total number of binding sites. There was no apparent correlation between the content of neurotensin-like immunoreactivity in the rat brain and the density of [3H]neurotensin binding sites in the various brain regions. The highest density of binding sites was found in the hypothalamus and the frontal cortex, intermediate levels in striatum, thalamus, midbrain, hippocampus and olfactory bulb, and low levels in cerebellum and pons-medulla oblongata. In general, there was less variation between different brain regions in the number of [3H]neurotensin binding sites than in the content of neurotensin-like immunoreactivity. The characteristics of this binding assay are consistent with [3H]neurotensin binding to a physiological receptor.

Animals↗
PubMed1984

Changes in substance P concentrations after protein synthesis inhibition provide an index of substance P utilization.

In all but one brain region sampled, substance P-like immunoreactivity (SPLI) was unchanged 4 h after a dose of cycloheximide that produced a near-total inhibition of rat brain protein synthesis. This suggests that brain substance P (SP) utilization is slow under basal conditions. The administration of the dopamine antagonist haloperidol to cycloheximide-pretreated rats apparently accelerated striatonigral SP utilization, as evidenced by large depletions in SPLI in the substantia nigra and striatum. Measuring the decline of SPLI a short time after protein synthesis inhibition may provide an index of brain SP utilization.

Animals↗
PubMed1984

Localization of specific neurotensin binding sites in the rat adrenal gland.

Specific tritiated neurotensin binding sites were localized in the rat adrenal gland by receptor autoradiography and characterized using a tissue homogenate receptor binding assay. High levels of specific neurotensin binding sites were found in the inner layer of the adrenal cortex and lower amounts in the adrenal medulla with only background labeling in the outer cortical layers. The structure-activity profile of the specific neurotensin binding was consistent with binding to a physiological neurotensin receptor.

Adrenal Glands↗
PubMed1984

Neurotensin in the rat anterior pituitary gland: effects of endocrinological manipulations.

Neurotensin-like immunoreactivity was detected by radioimmunoassay in the anterior lobe of the pituitary gland of several mammalian species, including man. In the rat, pituitary stalk transection did not change the content of neurotensin-like immunoreactivity. Surgical and chemical thyroidectomy produced a drastic reduction of neurotensin-like immunoreactivity in the anterior pituitary gland, whereas adrenalectomy and gonadectomy were without an effect and the decrease consequent to thyroidectomy was restricted to the pituitary gland. These results suggest an interaction between neurotensin and the hypothalamus/pituitary/thyroid axis at the level of the anterior pituitary gland.

Adrenal Glands↗
PubMed1984

Neurotensin receptors in the rat striatum: lesion studies.

The specific binding of [3H]neurotensin binding to the rat striatum was characterized and its localization investigated by using frontal cortex ablations and the neurotoxins kainic acid and 6-hydroxydopamine. Scatchard analysis indicated the existence of a single population of binding sites and the potencies of various neurotensin fragments in competing with [3H]neurotensin for its binding site were in good agreement with the potency values obtained in biological assays. The lesion studies indicated that more than 50% of striatal neurotensin receptors are localized on intrinsic neurones, approximately 30% on dopaminergic nerve terminals and 20% on corticostriatal nerve fibres.

Animals↗
PubMed1984

Neurotensin in human small cell lung carcinoma.

High levels of neurotensin-like immunoreactivity were found in human small cell lung carcinoma lines. No immunoreactivity was present in non-small cell carcinoma lines and only low amounts in postmortem human lung tissue. The immunoreactive material co-eluted with synthetic neurotensin on two different chromatographic systems. No evidence was obtained for the presence of specific neurotensin binding sites in any of the small cell carcinoma lines examined. The results suggest that small lung cell carcinoma lines may be useful for studying the biosynthesis of human neurotensin.

Carcinoma, Small Cell↗
PubMed1984

Biochemical and anatomical effects of antibodies against nerve growth factor on developing rat sensory ganglia.

The importance of nerve growth factor (NGF) for the development of sensory ganglia was investigated by injecting rat fetuses (16.50 days of gestation) with a single dose of anti-NGF antiserum. Four months later the treated animals showed a very large decrease in substance P- and somatostatin-like immunoreactivities in dorsal root ganglia and skin with a lesser decrease in trigeminal ganglia. Fluoride-resistant acid phosphatase, substance P-, and somatostatin-like immunoreactivities were greatly decreased in the dorsal horn of the spinal cord. No change in neurotensin- and [Met]enkephalin-like immunoreactivities was observed. The anti-NGF antiserum treatment produced a greater than 90% decrease in the number of unmyelinated dorsal root fibers and a 35% decrease in the total number of myelinated fibers. The loss in myelinated fibers was restricted to small-diameter fibers with no change in large-diameter fibers. No change in taste bud morphology was noted, thereby refuting the proposal that anti-NGF antiserum treatment may represent an animal model for familial dysautonomia. The present results indicate that NGF is a necessary requirement for the normal development of a significant population of prenatal rat dorsal root ganglion cells.

Aging↗
PubMed1984

Localization and actions of cholecystokinin in the rat pituitary neurointermediate lobe.

Rat pituitary neural lobe contained high concentrations of cholecystokinin-like immunoreactivity (CCK-LI). Section of the pituitary stalk resulted in loss of CCK-LI, and both lactation and replacement of drinking water with 2% saline resulted in marked depletion of CCK-LI. Rats with congenital diabetes insipidus (Brattleboro strain) had a 73% reduction in CCK-LI below the levels of hooded Long-Evans controls, where as levels in the brain were unchanged. Release of CCK-LI, labeled dopamine, and gamma-amino butyric acid in response to potassium depolarization was studied. There was a low fractional release of CCK-LI. Addition of sulfated CCK-8 (CCK-8s) to the medium enhanced the calcium-dependent potassium-stimulated release of dopamine, but basal release was unaffected. gamma-Amino butyric acid release was only poorly calcium dependent and not effected by extracellular CCK-8s. Vasopressin and oxytocin release were stimulated by electrical stimulation of the pituitary stalk, and were unaffected by the addition of CCK-8s to the medium. In vivo, however, the injection of 5 micrograms CCK-8s into the third ventricle resulted in increased plasma vasopressin concentrations.

Animals↗
PubMed1983

Mosaic distribution of neurotensin-like immunoreactivity in the cat striatum.

Neurotensin-like immunoreactivity was found in nerve fibers and terminals throughout the corpus striatum of the adult cat. The densest staining was observed in the globus pallidus followed by the caudate nucleus and the putamen. In the caudate nucleus neurotensin-like immunoreactivity had a patchy distribution which was in register with a similar pattern of enkephalin-like immunoreactivity.

Animals↗
PubMed1983

The regional distribution of neurotensin-like immunoreactivity in central and peripheral tissues of the cat.

The regional distribution of neurotensin-like immunoreactivity (NTLI) was studied by radioimmunoassay in central and peripheral tissues of the cat. In the brain, NTLI showed a wide distribution with highest concentrations in the hypothalamus, the caudate/putamen and the nucleus accumbens. Only low levels of NTLI were measured in the spinal cord and there was no difference between dorsal and ventral horn. In the periphery, NTLI was present in high concentrations in the adrenal medulla and in lower amounts in the superior cervical and the ciliary ganglion. NTLI was present in both lobes of the pituitary gland and throughout the gastrointestinal tract with high concentrations in the ileum. All other peripheral tissues tested contained low but detectable amounts of NTLI. Gel chromatography on Sephadex G-25 was used in order to characterize the immunoreactive material; NTLI in tissue extracts from 3 central and 3 peripheral tissues co-eluted in a single peak at the position of synthetic neurotensin. NTLI is widely distributed throughout cat tissues and there are important differences from the distribution pattern in the rat, the only other species examined in detail to date.

Animals↗