Showing papers by "Michel Goedert published in 1984"
TL;DR: In this article, the authors investigated the distribution of 3H-labeled substance P binding sites within various rat brain regions and correlated this with the rate of substance P-induced hydrolysis of inositol phospholipids in the same areas of the CNS.
Abstract: The undecapeptide substance P is a neurotransmitter candidate in the mammalian central and peripheral nervous system. Although the distribution of substance P-like immunoreactivity within the central nervous system (CNS) is well established, the recent identification and autoradiographic localization of specific substance P-binding sites has revealed numerous areas of mismatch between peptide levels and numbers of such sites. Previous studies have shown that substance P stimulates the hydrolysis of inositol phospholipids in peripheral tissues and in the hypothalamus, probably through stimulation of a polyphosphoinositide-specific phospholipase C (refs 9-11). Inositol phospholipid hydrolysis has been implicated in the mobilization of cytosolic calcium following receptor activation in several neurotransmitter and hormonal systems. We have therefore investigated the distribution of 3H-labelled substance P binding sites within various rat brain regions and correlated this with the rate of substance P-induced hydrolysis of inositol phospholipids in the same areas of the CNS. We found that the rate of inositol phospholipid hydrolysis was proportional to the number of binding sites specific for 3H-substance P, suggesting that binding sites revealed by 3H-substance P autoradiography correspond to functional substance P receptors.
160 citations
TL;DR: It is indicated that NGF is a necessary requirement for the normal development of a significant population of prenatal rat dorsal root ganglion cells and skin with a lesser decrease in trigeminal ganglia.
Abstract: 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.
121 citations
TL;DR: 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.
115 citations
TL;DR: There was less variation between different brain regions in the number of [3H]neurotensin binding sites than in the content of neurotensin-like immunoreactivity in the rat brain, and the density of binding sites was found in the various brain regions.
107 citations
TL;DR: Low density is found in the neurotensin-rich striosomes and a high density in the neuron-poor surrounding tissue in mammals that has been localized in the cat caudate nucleus by autoradiography.
Abstract: The adult corpus striatum in mammals is divided into distinct histochemical compartments1. If the cat caudate nucleus is stained for acetylcholinesterase a number of macroscopically visible zones appear that have lower acetylcholinesterase activity than the surrounding tissue2. These patches, called ‘striosomes’1, correspond to regions of high [Met]-enkephalin-like immunoreactivity3 and dense opiate receptor binding4 and are related to the uneven distribution of striatal efferent neurones and cortical afferent terminations5,6. One of the highest concentrations of neurotensin-like immunoreactivity is in the striatum and the immunoreactive material co-elutes with synthetic neurotensin on gel chromatography7. Recently, we have found that neurotensin-like immunoreactivity in the cat caudate nucleus coincides with the striosomes8. We have now localized neurotensin receptors in the cat caudate nucleus by autoradiography9 and found low density in the neurotensin-rich striosomes and a high density in the neurotensin-poor surrounding tissue.
73 citations
TL;DR: 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.
70 citations
TL;DR: It is reported that the majority of specific 3H-neurotensin binding sites is present in the guinea pig ileum circular smooth muscle layer, indicating a direct relationship between the effects of neurotensin and of nerve stimulation.
Abstract: Neurotensin is a 13-amino acid peptide that is widely distributed in central and peripheral tissues of various mammalian species1. In peripheral tissues, the highest concentration of neurotensin-like immunoreactivity is found in the ileum, where it is present in endocrine-like cells and nerve fibres2–4. The longitudinal smooth muscle layer of the guinea pig ileum, where neurotensin has both a direct relaxant and an indirect contractile action, has been used extensively as a biological assay system for neurotensin5. We report here that the majority of specific 3H-neurotensin binding sites is present in the guinea pig ileum circular smooth muscle layer, which is known to be innervated by a large proportion of the ileal non-adrenergic inhibitory nerves6. Neurotensin produces a dose-dependent, tetrodotoxin-resistant relaxation, whereas the relaxation produced by field stimulation of the inhibitory nerves is frequency-dependent and tetrodotoxin-sensitive. The calcium-dependent potassium channel blocker apamin7,8 inhibits both the neurotensin- and nerve stimulation-induced muscle relaxation. Incubation of the circular smooth muscle preparation with a neurotensin antiserum substantially inhibited the nerve stimulation-induced relaxation, indicating a direct relationship between the effects of neurotensin and of nerve stimulation.
59 citations
49 citations
TL;DR: The accumulating evidence for neurotensin's role as a neurotransmitter is assessed and Michel Goedert assesses the accumulating evidence.
34 citations
TL;DR: High levels of neurotensin-like immunoreactivity were found in human small cell lung carcinoma lines, and the immunoreactive material co-eluted with synthetic neurotensIn on two different chromatographic systems, suggesting that small lung cell carcinomas lines may be useful for studying the biosynthesis of human neurotENSin.
Abstract: 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.
25 citations
TL;DR: XPLI was found in a variety of peripheral tissues of the rat and it coeluted with synthetic neurotensin on reverse phase high-performance liquid chromatography, and is probably present in preganglionic parasympathetic nerve fibres.
TL;DR: Results suggest an interaction between neurotensin and the hypothalamus/pituitary/thyroid axis at the level of the anterior pituitary gland.
TL;DR: 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, however, the injection of 5 micrograms CCK8s into the third ventricle resulted in increased plasma vasopress in concentrations.
Abstract: 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, whereas levels in the brain were unchanged. Release of CCK-LI, labeled dopamine, and γ-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. γ-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 CC...
TL;DR: 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, suggesting that brain substance P (SP) utilization is slow under basal conditions.
TL;DR: Specific tritiated neurotensin binding sites were localized in the rat adrenal gland by receptor autoradiography and characterized using a tissue homogenate receptor binding assay, consistent with binding to a physiological neurotensIn receptor.