Substance P receptors in primary cultures of cortical astrocytes from the mouse.

Torrens, Y.; Beaujouan, J. C.; Saffroy, M.; Montety, M C Daguet de; Bergström, Lena; Głowiński, J.

doi:10.1073/pnas.83.23.9216

Cited by 79 publications

(31 citation statements)

References 28 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present report, we have demonstrated that after optic nerve transection, substance P binding sites are expressed in high concentrations by cells comprising the glial scar in the optic nerve and optic tract. These data are consistent with previous in vitro studies that demonstrated that substance P receptors are present in 2-to 3-week-old primary cultures of cortical astrocytes from newborn mice and that addition of substance P to these astrocyte cultures stimulates phosphatidylinositol turnover (16). Substance P has also been shown to stimulate the cyclooxygenase pathway of arachidonic acid metabolism in 2-to 3-week-old cultures of rat astrocytes and to evoke the formation of prostaglandin E and thromboxane B2 in a dose-dependent manner (13).…”

Section: Resultssupporting

confidence: 82%

Substance P receptor binding sites are expressed by glia in vivo after neuronal injury.

Mantyh

Johnson

Boehmer

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

In vitro studies have demonstrated that glia can express functional receptors for a variety of neurotransmitters. To determine whether similar neurotransmitter receptors are also expressed by glia in vivo, we examined the glial scar in the transected optic nerve of the albino rabbit by quantitative receptor autoradiography. Receptor binding sites for radiolabeled calcitonin gene-related peptide, cholecystokinin, galanin, glutamate, somatostatin, substance P, and vasoactive intestinal peptide were examined. Specific receptor binding sites for each ofthese neurotransmitters were identified in the rabbit forebrain but were not detected in the normal optic nerve or tract. In the transected optic nerve and tract, only receptor binding sites for substance P were expressed at detectable levels. The density of substance P receptor binding sites observed in this glial scar is among the highest observed in the rabbit forebrain. Ligand displacement and saturation experiments indicate that the substance P receptor binding site expressed by the glial scar has pharmacological characteristics similar to those of substance P receptors in the rabbit striatum, rat brain, and rat and canine gut. The present study demonstrates that glial cells in vivo express high concentrations of substance P receptor binding sites after transection of retinal ganglion cell axons. Because substance P has been shown to regulate inflammatory and immune responses in peripheral tissues, substance P may also, by analogy, be involved in regulating the glial response to injury in the central nervous system.A major question in neurobiology is why damaged mammalian central nervous system (CNS) neurons do not regenerate in vivo. In recent years, the focus ofattention has shifted from CNS neurons themselves, which appear to have the capacity to regenerate, to CNS glia, which apparently inhibit the regrowth of axons in the CNS. Thus, it has been demonstrated that, after injury, regenerating axons grow a short distance until they reach the glial scar, at which time they appear to stop growing and degenerate (1-6). The major cellular constituent of a CNS glial scar is the reactive astrocyte (4). Unlike fibroblasts, which form scars in nonneural tissue by secreting large amounts of collagenous extracellular matrix, astrocytes form scars by extending numerous processes that become packed with intracellular glial filaments (7). Astrocytes proliferate in response to injury (8), and it appears that these "reactive astrocytes" are biochemically different from the major class of astrocytes present in the normal nonlesioned brain (4). Recently, several neuropeptides, including bombesin, substance K, and substance P, have been shown to be mitogenic (9, 10) for several cell types that may be involved in the inflammatory and wound-healing responses in peripheral tissues (11). In vitro studies suggest that glia are potential targets for a variety of neurotransmitters (12) including substance P (13-16), somatostatin (17, 18), and vasoactive intestinal peptide (15,17...

show abstract

Section: Resultssupporting

confidence: 82%

Substance P receptor binding sites are expressed by glia in vivo after neuronal injury.

Mantyh

Johnson

Boehmer

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…In contrast to its absence of effect on these peripheral targets, SP has been confirmed in this study, in a cellular model representative of astrocytes of the central nervous system, as a very effective inducing or potentiating agent of this type of mediators. Functional SP receptors have been identified in mouse and rat primary astrocytes [30,31] and enhanced secretion of inflammatory cytokines has been demonstrated upon SP stimulation of these cells [32,33]. This indicates that the pro-inflammatory effect of SP observed on astrocytoma cell lines can be extended to normal primary astrocytes.…”

Section: Discussio•mentioning

confidence: 76%

Effect of substance P on cytokine production by human astrocytic cells and blood mononuclear cells: characterization of novel tachykinin receptor antagonists

et al. 1996

View full text Add to dashboard Cite

Substance P (SP) has been reported to induce inflammatory cytokine production in human neuroglial cells and peripheral lymphoid cells as well. In order to evaluate the potency of novel non-peptide antagonists of the tachykinin receptors as inhibitors of SP-induced cytokines, we used the astrocytoma cell line U373MG and blood mononuclear cells as models of central and peripheral SP-target cells, respectively. In tlk. first part of this study, we showed that SR 140333, an NKI tachykinin receptor antagonist, was able to inhibit strongly the SP-indoced production of interleukin (IL)-6 and IL-8 in the astrocytoma cell line. The antagonistic activity of SR 140333 toward SP-induced cytokine production was specific and could not be attributed to a general anti-cytokine effect, since cytokine release induced by another inflammatory protein such as IL-I~ was not blocked by this compound. In addition, NK2 and NK3 agonist neuropeptides were at least 1000-fold less effective than SP, while SR 48968 and SR 142801 which are selective NK2 and NK3 receptor antagonists, respectively, displayed a 2.5-3 orders of magnitude lower inhibitory potency than SR 140333. All these data indicated that SR 140333 blocked SP-induced cytokine production in U373MG astrocytic cells via a specific NKI receptor-mediated process. Since SP has also been described to trigger peripheral blood mononuclear cells (PBMNC) or monocytes to release inflammatory cytokines, we attempted, in the second part of this study, to evaluate the potential antagonistic effect of our compounds on these cells. Experiments oil human PBMNC from different donors were carried out to determine first their pattern of cytokine production upon SP stimulation. Surprisingly, we noticed that SP at concentrations ranging from 0.I to I000 nM was unable to stimulate the release of any inflammatory cytokine tested. This raises the question of the specificity of the reported in vitro effects of SP on cytokine production by human peripheral immune cells.

show abstract

“…Evidence exists that amino acids are released by high-K+ solution in a Ca*+-independent manner (Drejer et al, 1982(Drejer et al, , 1983 and that astrocytes may be intimately involved in neurotransmission processes, amino acid uptake (Hertz and Schousboe, 1986;Hijsli et al, 1986) and they possess receptors for amino acid transmitters (Glu, Asp, GABA) and peptides (Bowman and Kimelberg, 1984;Kettermann and Schachner, 1985;Hamprecht, 1986;Torrens et al, 1986). Binding sites for SP were detected on glial cells of the spinal cord and SP enhances accummulation of labeled inositol phosphates in cultures of cortical glial cells from the mouse (Torrens et al, 1986). In addition, synthetic human calcitonin raises intracellullar concentration of cyclic AMP in rat astroglia cells (Hamprecht, 1986).…”

Section: Aspmentioning

confidence: 99%

Tachykinins and calcitonin gene-related peptide enhance release of endogenous glutamate and aspartate from the rat spinal dorsal horn slice

1990

View full text Add to dashboard Cite

The effects of dorsal root stimulation and of substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP) on the basal release of 9 endogenous amino acids, including glutamate (Glu) and aspartate (Asp), have been investigated using the rat spinal cord slice-dorsal root ganglion preparation and high-performance liquid chromatography with fluorimetric detection. High-intensity repetitive electrical stimulation of a lumbar dorsal root produced a Ca2(+)- dependent increase in the basal release of Asp, Glu, glycine (Gly), serine (Ser), and threonine (Thr). Low concentrations of SP (2 x 10(-7) M) caused a selective increase in the rate of basal release of Glu, whereas higher concentrations (1–5 x 10(-6) M) produced, in addition, an increase in the basal release of Asp. The SP-induced increase of Glu persisted in the absence of external Ca2+, but the effect was blocked by (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-SP, an SP analog claimed to be an antagonist of the synthetic SP. NKA (5 x 10(-7) - 10(-6) M), a related tachykinin coexpressed with SP in primary sensory neurons, enhanced the basal release of Gly. CGRP (10(-7) M) caused a significant, largely Ca2(+)-independent increase in the basal release of Glu and Asp and a decrease in asparagine. SP and CGRP potentiated the electrically evoked release of Glu and Asp. Neonatal capsaicin treatment did not significantly alter the basal efflux of 9 endogenous amino acids from the spinal slices, but it prevented the dorsal root stimulation-evoked release of Asp, Glu, Gly, and Thr and the SP-induced increase in the basal release of Glu. However, the effect of CGRP was not significantly modified by the capsaicin treatment. These results indicate that tachykinins (SP and NKA) and CGRP are capable of modulating the basal and electrically evoked release of endogenous Glu and Asp, and these actions may provide an important mechanism by which the peptides contribute to the regulation of the primary afferent synaptic transmission. The enhancement of the basal and the dorsal root stimulation-evoked release of Glu and Asp by tachykinins and CGRP may have important physiological implications for strengthening the synaptic connections in the spinal dorsal horn.

show abstract

Substance P receptors in primary cultures of cortical astrocytes from the mouse.

Cited by 79 publications

References 28 publications

Substance P receptor binding sites are expressed by glia in vivo after neuronal injury.

Substance P receptor binding sites are expressed by glia in vivo after neuronal injury.

Effect of substance P on cytokine production by human astrocytic cells and blood mononuclear cells: characterization of novel tachykinin receptor antagonists

Tachykinins and calcitonin gene-related peptide enhance release of endogenous glutamate and aspartate from the rat spinal dorsal horn slice

Contact Info

Product

Resources

About