Substance P receptors in the human spinal cord: decrease in amyotrophic lateral sclerosis

Dietl, M.; Sánchez, María Jesús Torquemada; Probst, A.; Palacios, J. M.

doi:10.1016/0006-8993(89)90032-2

Cited by 38 publications

(8 citation statements)

References 31 publications

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“…This generally corresponds with the temporal profile of various receptor binding sites described earlier in adult rat and/or human spinal cord (Lamotte et al, 1976;Ninkovic et al, 1981;Charlton and Helke, 1985;Gouarderes et al, 1985Gouarderes et al, , 1991Mantyh and Hunt, 1985;Buck et al, 1986;Skofitsch et al, 1986;Faull and Villiger, 1987;Dietl et al, 1989;Faull et al, 1989;Besse et al, 1991;Stevens et al, 1991;Yashpal et al, 1991aYashpal et al, ,b, 1992Kar et al, 1994). The dorsal horn, particularly laminae I and 11, in all segments of the spinal cord, was found to be enriched with NK-1, NK-3, popioid, L12511gala-nin, [1251]neurotensin, [1251JToD8-SRIF14 and[12511VIP receptor (Garry et al, 1991;Yashpal et al, 1992).…”

Section: Functional Significancesupporting

confidence: 73%

“…Alternatively, reductions in peptide-receptor binding sites may result in response to decrease in the capacity of neurons and/or glial cells to synthesize these receptor proteins. The phenomenon of neuronal elimination which occurs in the developing spinal cord is unlikely to be associated with the decline of the receptor binding sites, since large-scale cell death (E15-Pl) preceeds the losses in P-immunoreactive terminals Dietl et al, 1989). These findings have been recently reinforced using immunocytochemical and/or in situ hybridization techniques which showed the presence of NK1 receptor mRNA as well as the protein in neurons (and the dendrites in case of protein) of the dorsal spinal cord.…”

Section: Anatomical Correlationmentioning

confidence: 99%

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Neuropeptide receptors in developing and adult rat spinal cord: An in vitro quantitative autoradiography study of calcitonin gene‐related peptide, neurokinins, μ‐opioid, galanin, somatostatin, neurotensin and vasoactive intestinal polypeptide receptors

Kar

Quirion

1995

J of Comparative Neurology

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A number of neuroactive peptides including calcitonin gene-related peptide (CGRP), substance P, neurokinin B, opioids, somatostatin (SRIF), galanin, neurotensin and vasoactive intestinal polypeptide (VIP) have been localized in adult rat spinal cord and are considered to participate either directly and/or indirectly in the processing of sensory, motor and autonomic functions. Most of these peptides appear early during development, leading to the suggestion that peptides, in addition to their neurotransmitter/neuromodulator roles, may possibly be involved in the normal growth and maturation of the spinal cord. To provide an anatomical substrate for a better understanding of the possible roles of peptides in the ontogenic development of the cord, we investigated the topographical profile as well as variation in densities of [125I]hCGRP alpha, [125I]substance P/neurokinin-1 (NK-1), [125I]eledoisin/neurokinin-3 (NK-3), [125I]FK 33-824 ([D-Ala2, Me-Phe4, Met(O)ol5]enkephalin)/mu-opioid, [125I]galanin, [125I]T0D8-SRIF14 (an analog of somatostatin); [125I]neurotensin and [125I]VIP binding sites in postnatal and adult rat spinal cord using in vitro quantitative receptor autoradiography. Receptor binding sites recognized by each radioligand are found to be distributed widely during early stages of postnatal development and then to undergo selective modification to attain their adult profile of distribution during the third week of postnatal development. The apparent density of various receptor sites, however, are differently regulated depending on the lamina and the stage of development studied. For example, the density of mu-opioid binding sites, following a peak at postnatal day 4 (P4), declines gradually in almost all regions of the spinal cord with the increasing age of the animal. [125I]substance P/NK-1 binding sites, on the other hand, show very little variation until P14 and then subsequently decrease as the development proceeds. In the adult rat, most of these peptide receptor binding sites are localized in relatively high amounts in the superficial laminae of the dorsal horn. To varying extents, moderate to low density of various peptide receptor binding sites are also found to be present in the ventral horn, intermediolateral cell column and around the central canal. Taken together, these results suggest that each receptor-ligand system is regulated differently during development and may each uniquely be involved in cellular growth, differentiation and in maturation of the normal neural circuits of the spinal cord. Furthermore, the selective localization of various receptor binding sites in adult rat spinal cord over a wide variety of functionally distinct regions reinforces the neurotransmitter/modulator roles of these peptides in sensory, motor and autonomic functions associated with the spinal cord.

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Section: Functional Significancesupporting

confidence: 73%

Section: Anatomical Correlationmentioning

confidence: 99%

Neuropeptide receptors in developing and adult rat spinal cord: An in vitro quantitative autoradiography study of calcitonin gene‐related peptide, neurokinins, μ‐opioid, galanin, somatostatin, neurotensin and vasoactive intestinal polypeptide receptors

Kar

Quirion

1995

J of Comparative Neurology

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“…NK-1R has been found to be reduced in the ventral horn of the spinal cord in patients with ALS (Dietl et al, 1989). We tested whether the expression of NK-1R is reduced in mSOD1 G93A mice.…”

Section: L-nat Inhibits the Downregulation Of Nk-1rmentioning

confidence: 99%

N-acetyl-l-tryptophan delays disease onset and extends survival in an amyotrophic lateral sclerosis transgenic mouse model

Fotinos

et al. 2015

Neurobiology of Disease

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Data suggest the potential of L-NAT as a novel therapeutic strategy for ALS and provide insight into its action mechanisms. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron loss, while inflammation has been implicated in its pathogenesis. Both inhibitors of cytochrome c release and antagonists of the neurokinin 1 receptor (NK-1R) have been reported to provide neuroprotection in ALS and/or other neurodegenerative diseases by us and other researchers. However, whether N-acetyl-L-tryptophan (L-NAT), an inhibitor of cytochrome c release and an antagonist of NK-1R, provides neuroprotection in ALS remains unknown. Here we demonstrate that the administration of L-NAT delayed disease onset, extended survival, and ameliorated deteriorations in motor performance in mSOD1(G93A) ALS transgenic mice. Our data showed that L-NAT reached the spinal cord, skeletal muscle, and brain. In addition, we demonstrate that L-NAT reduced the release of cytochrome c/smac/AIF, increased Bcl-xL levels, and inhibited the activation of caspase-3. L-NAT also ameliorated motor neuron loss and gross atrophy, and suppressed inflammation, as shown by decreased GFAP and Iba1 levels. Furthermore, we found gradually reduced NK-1R levels in the spinal cords of mSOD1(G93A) mice, while L-NAT treatment restored NK-1R levels. We propose the use of L-NAT as a potential therapeutic invention against ALS.

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“…In the ventraI horn of MND patients reduction in acetyleholinesterase, choiine acetyltransferase and in muscarinie, benzodiazepine, glycinergie, TRH and substance P receptoTS have been described (Whitehouse et al 1983;Manaker et al 1988;Dietl et al 1989). However, there is no change in the concentration of [3-adrenergic receptors or in the norepinephrine sites.…”

Section: Motor Neuron Diseasementioning

confidence: 99%

Clinical Pharmacology of Motor Neurons

Guiloff¹

1995

Motor Neuron Disease

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Substance P receptors in the human spinal cord: decrease in amyotrophic lateral sclerosis

Cited by 38 publications

References 31 publications

Neuropeptide receptors in developing and adult rat spinal cord: An in vitro quantitative autoradiography study of calcitonin gene‐related peptide, neurokinins, μ‐opioid, galanin, somatostatin, neurotensin and vasoactive intestinal polypeptide receptors

Neuropeptide receptors in developing and adult rat spinal cord: An in vitro quantitative autoradiography study of calcitonin gene‐related peptide, neurokinins, μ‐opioid, galanin, somatostatin, neurotensin and vasoactive intestinal polypeptide receptors

N-acetyl-l-tryptophan delays disease onset and extends survival in an amyotrophic lateral sclerosis transgenic mouse model

Clinical Pharmacology of Motor Neurons

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