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Biomedical subjects

M Goedert

Publications and source records attributed to M Goedert.

At least 91 records · Page 5Linked to original sources

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

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

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

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

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

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

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

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

The regional distribution and chromatographic characterisation of neurotensin-like immunoreactivity in the rat central nervous system.

Carboxy- and amino-terminal specific neurotensin antisera have been characterized and used to determine the nature of neurotensin-like immunoreactivity in the rat central nervous system. Using these antisera, together with the separation of neurotensin-like immunoreactivity on reverse-phase HPLC columns, it is clear that the majority of rat central nervous system neurotensin-like immunoreactivity is indistinguishable from the synthetic tridecapeptide, However, smaller amounts of carboxy- and amino-terminal neurotensin-like immunoreactivity were detected, which may correspond to carboxy- and amino-terminal fragments of neurotensin. In addition, using the amino-terminal directed neurotensin antiserum, a detailed distribution of neurotensin-like immunoreactivity in the rat central nervous system is described. Highest amounts were found in the hypothalamus, central amygdaloid nucleus, bed nucleus of the stria terminalis and the substantia gelatinosa of the spinal cord and of the trigeminal region.

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