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Biomedical subjects

M Goedert

Publications and source records attributed to M Goedert.

At least 55 records · Page 3Linked to original sources

Neurotensin-like immunoreactivity and neurotensin receptors in the rat hypothalamus and in the neurointermediate lobe of the pituitary gland.

In the rat hypothalamus, cell bodies containing neurotensin-like immunoreactivity were mainly found in the medial preoptic area, the periventricular nucleus, the paraventricular nucleus, the supraoptic nucleus and the arcuate nucleus. [3H]neurotensin binding sites were observed throughout the hypothalamus with a dense accumulation of silver grains over the paraventricular nucleus, the arcuate nucleus and the median eminence region. By radioimmunoassay neurotensin-like immunoreactivity was also found in the neurointermediate lobe of the pituitary gland of various mammalian species and in human postmortem posterior pituitary glands. In the rat studies involving pituitary stalk transections and the neurotoxin monosodium glutamate indicated the presence of a neurotensinergic pathway from the arcuate nucleus to the neurointermediate lobe of the pituitary gland. [3H]neurotensin binding sites were found to be concentrated over the intermediate lobe of the pituitary gland and their presence was not affected by pituitary stalk transection, indicating their localization on endocrine cells of the intermediate lobe of the pituitary gland.

Animals

Neurotensin in human brain: regional distribution and effects of neurological illness.

The regional distribution of neurotensin-like immunoreactivity was investigated in normal human brain and in brains of patients who had died with neurological illness. In Huntington's disease, neurotensin was increased in the pallidum, whilst in Parkinson's disease no significant changes in neurotensin content were observed. Similarly no changes were found in the telencephalic neurotensin content in senile dementia of the Alzheimer type. High levels of neurotensin-like immunoreactivity were detected in lumbar cerebrospinal fluid from patients and the characterization of the immunoreactive material by high-performance liquid chromatography showed it to be indistinguishable from synthetic neurotensin.

Aged

The comparative distribution of [Lys8-Asn9]-neurotensin8-13-like immunoreactivity in chicken and rat tissues.

The presence of [Lys8-Asn9]-neurotensin8-13-like immunoreactivity was studied by radioimmunoassay in chicken and rat tissues. In the chicken, [Lys8-Asn9]-neurotensin8-13-like immunoreactivity showed a wide distribution throughout the central nervous system and the gastrointestinal tract, and the immunoreactive material co-eluted with the synthetic peptide on reverse-phase high performance liquid chromatography. In the rat, [Lys8-Asn9]-neurotensin8-13-like immunoreactivity was widely distributed when 0.1 M HCl was used as the extraction procedure. However, the immunoreactive material did not co-elute with the synthetic peptide on reverse-phase high performance liquid chromatography; moreover, the addition of the aspartic proteinase inhibitor pepstatin to the extraction medium resulted in a large reduction in the levels of [Lys8-Asn9]-neurotensin8-13-like immunoreactivity and no immunoreactive material could be detected when the tissues were extracted using acetone/HCl. The present results therefore indicate that [Lys8-Asn9]-neurotensin8-13-like immunoreactivity is not present in rat tissues. That which was detected resulted from an extraction artefact.

Animals

The effects of chronic neuroleptic treatment on neurotensin-like immunoreactivity in the rat central nervous system.

The dopamine receptor antagonist fluphenazine decanoate, when administered for a total period of 10 months, produced a large increase in neurotensin-like immunoreactivity in dopamine-rich brain areas, such as the nucleus accumbens, the striatum and the frontal cortex. A smaller, non-significant increase was observed in the substantia nigra with no change in either the hypothalamus or the spinal cord. The present results provide further evidence in favour of a functional interaction between neurotensin and dopamine in the central nervous system.

Animals

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

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

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

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

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

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

Dose-dependent effects of capsaicin on primary sensory neurons in the neonatal rat.

The numbers of myelinated and unmyelinated fibers were counted in dorsal roots of adult rats treated neonatally with capsaicin in doses ranging from 5 to 100 mg/kg. Substance P and somatostatin levels in the spinal cord, dorsal roots, and sensory ganglia also were determined in control and treated animals. Capsaicin administration lead to the loss of both small myelinated and unmyelinated fibers from dorsal roots. However, whereas a near total loss, up to 94%, of unmyelinated fibers was achieved after high doses of capsaicin, the reduction of myelinated fibers, even of the smallest caliber, did not exceed 40%. The degree of fiber loss showed a clear dose dependency, with little detectable damage to myelinated fibers at doses of less than 50 mg/kg and with an ED50 for damage to unmyelinated fibers of 5 to 10 mg/kg. In all of the structures examined, particularly the dorsal roots, a roughly parallel decrease of substance P and somatostatin was found with capsaicin dose. The depletions of spinal cord substance P (55%) and somatostatin (20%) produced by neonatal capsaicin treatment were similar to those produced by dorsal rhizotomy. Capsaicin does not appear to be specific for primary afferents containing either substance P or somatostatin.

Animals

The origin of substance P in the rat submandibular gland and its major duct.

The origin of the substance P-like immunoreactivity in the rat submandibular gland and its major duct was investigated. Lesions severing the sympathetic, pre- and postganglionic parasympathetic and sensory innervation of the submandibular gland, or treatment with the neurotoxin capsaicin produced only a small non-significant decrease in the substance P-like immunoreactivity content of the gland. In contrast both sensory denervation and capsaicin treatment produced a substantial decrease in the content of substance P-like immunoreactivity in the major duct of the submandibular gland. These observations indicate that the duct innervation is clearly of sensory origin, whilst the substance P-like immunoreactivity of the gland itself appears to be intrinsic.

Animals

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

The nature of the substance P-containing nerve fibres in taste papillae of the rat tongue.

The nature of the association of substance P (SP) with taste buds in the rat tongue was investigated by immunohistochemical and radioimmunoassay techniques. Both the circumvallate and fungiform papillae were found to receive a rich innervation by substance P-containing fibres. Although these fibres were closely associated with the taste buds in these structures, they assumed a perigemmal rather than an intragemmal location. Bilateral lesions of the glossopharyngeal nerve resulted in the depletion of taste buds from the vallate papilla and a large reduction in substance P immunoreactive fibres in this area. Lesions of the chorda tympani, which led to the degeneration of taste buds in fungiform papillae, had no effect on the immunohistochemical appearance of substance P in these papilla or on the substance P levels in the anterior part of the tongue. Lesions of the mandibular division of the trigeminal nerve or neonatal capsaicin treatment had no effect on the structural integrity of taste buds in fungiform papillae but led to the depletion of substance P-immunoreactive fibres from these papillae. Both of these procedures caused a 71% reduction in the substance P content of the anterior tongue, ipsilaterally after the nerve lesion and bilaterally after capsaicin treatment. The results are discussed in relation to the possible functional role of substance P-containing fibres within nerves supplying taste structures of the tongue.

Animals

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

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

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