共查询到20条相似文献,搜索用时 15 毫秒
1.
Chen GT Yang M Song Y Lu ZQ Zhang JQ Huang HL Wu LJ Guo DA 《Applied microbiology and biotechnology》2008,77(6):1345-1350
Preparative-scale fermentation of ginsenoside Rb1 (1) with Acremonium strictum AS 3.2058 gave three new compounds, 12β-hydroxydammar-3-one-20 (S)-O-β-d-glucopyranoside (7), 12β, 25-dihydroxydammar-(E)-20(22)-ene-3-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside (8), and 12β, 20 (R), 25-trihydroxydammar-3-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside (9), along with five known compounds, ginsenoside Rd (2), gypenoside XVII (3), ginsenoside Rg3 (4), ginsenoside F2 (5), and compound K (6). The structural elucidation of these metabolites was based primarily on one- and two-dimensional nuclear magnetic resonance
and high-resolution electron spray ionization mass spectra analyses. Among these compounds, 2–6 are also the metabolites of ginsenoside Rb1 in mammals. This result demonstrated that microbial culture parallels mammalian metabolism; therefore, A. strictum might be a useful tool for generating mammalian metabolites of related analogs of ginsenosides for complete structural identification
and for further use in pharmaceutical research in this series of compounds. In addition, the biotransformation kinetics was
also investigated. 相似文献
2.
Extracellular ATP triggers changes in intracellular Ca2+, ion channel function, and membrane trafficking in adipocytes. The aim of the present study was to determine which P2 receptors
might mediate the Ca2+ signaling and membrane trafficking responses to ATP in brown fat cells. RT-PCR was used to determine which P2 receptors are
expressed in brown fat cells. Responses to nucleotide agonists and antagonists were characterized using fura-2 fluorescence
imaging of Ca2+ responses, and FM 1-43 fluorescence imaging and membrane capacitance measurements to assess membrane trafficking. The pharmacology
of the Ca2+ responses fits the properties of the P2Y receptors for which mRNA is expressed, but the agonist and antagonist sensitivity
of the membrane-trafficking response was not consistent with any P2 receptor described to date. Brown adipocytes expressed
mRNA for P2Y2, P2Y6, and P2Y12 metabotropic receptors and P2X1, P2X2, P2X3, P2X4, P2X5, and P2X7 ionotropic receptors. The agonists ATP, ADP, UTP, UDP and 2′, 3′-(benzoylbenzoyl) ATP (BzATP) increased intracellular Ca2+, while 100 μM suramin, pyridoxal-phosphate-6-azophenyl-2′ 4′-disulfonic acid (PPADS), or Reactive Blue 2 partially blocked Ca2+ responses. ATP, but not ADP, UTP, UDP or BzATP activated membrane trafficking. The membrane response could be blocked completely
with 1 μM PPADS but not by the antagonist MRS2179. We conclude that multiple P2 receptors mediate the ATP responses of brown fat cells,
and that membrane trafficking is regulated by a P2 receptor showing unusual properties. 相似文献
3.
P2X<Subscript>2</Subscript> and P2X<Subscript>3</Subscript> purinoceptors in the rat enteric nervous system 总被引:3,自引:3,他引:0
Adenosine 5-triphosphate receptors are known to be involved in fast excitatory postsynaptic currents in myenteric neurons of the digestive tract. In the present study, the distribution of P2X2 and P2X3 receptor mRNA was examined by in situ hybridisation while P2X2 and P2X3 receptor protein was localised by immunohistochemical methods. In addition, P2X2 and P2X3 receptors were colocalised with calbindin and calretinin in the myenteric and submucosal plexus. P2X2- and P2X3-immunoreactive neurons were found in the myenteric and submucosal plexuses throughout the entire length of the rat digestive tract from the stomach to the colon. Approximately 60%, 70% and 50% of the ganglion cells in the myenteric plexus of the gastric corpus, ileum and distal colon, and 56% and 45% in the submucosal plexus of the ileum and distal colon, respectively, showed positive immunoreactivity to the P2X2 receptor. Approximately 10%, 2% and 15% of the ganglion cells in the myenteric plexus of the gastric corpus, ileum and distal colon, and 62% and 40% in the submucosal plexus of the ileum and distal colon, respectively, showed positive immunoreactivity to the P2X3 receptor. Double-labelling studies showed that about 10–25% of the neurons with P2X2 immunoreactivity in myenteric plexus and 30–50% in the submucosal plexus were found to express calbindin or calretinin. About 80% of the neurons with P2X3 receptor immunoreactivity in the myenteric plexus and about 40% in the submucosal plexus expressed calretinin. Approximately 30–75% of the neurons with P2X3 receptor immunoreactivity in the submucosal plexus expressed calbindin, while none of them were found to express calbindin in the myenteric plexus. 相似文献
4.
The distribution of P2Y2 receptor-immunoreactive (ir) neurons and fibers and coexistence of P2Y2 with P2X2 and P2X3 receptors, neuropeptide Y (NPY), calretinin (CR), calbindin (CB) and nitric oxide synthase (NOS) was investigated with immunostaining
methods. The results showed that P2Y2-ir neurons and fibers were distributed widely in myenteric and submucous plexuses of the guinea pig stomach corpus, jejunum,
ileum and colon. The typical morphology of P2Y2-ir neurons was a long process with strong positive staining on the same side of the cell body. The P2Y2-ir neurons could be Dogiel type 1. About 40–60% P2X3-ir neurons were immunoreactive for P2Y2 in the myenteric plexus and all the P2X3-ir neurons expressed the P2Y2 receptor in the submucosal plexus; almost all the NPY-ir neurons and the majority of CR-ir neurons were also immunoreactive
for P2Y2, especially in the myenteric plexus of the small intestine; no P2Y2-ir neurons were immunoreactive for P2X2 receptors, CB and NOS. It is shown for the first time that S type/Dogiel type 1 neurons with fast P2X and slow P2Y receptor-mediated
depolarizations could be those neurons expressing both P2Y2-ir and P2X3-ir and that they are widely distributed in myenteric and submucosal plexuses of guinea pig gut. 相似文献
5.
6.
Development of nerves expressing P2X<Subscript>3</Subscript> receptors in the myenteric plexus of rat stomach 总被引:4,自引:2,他引:2
Development of neurones and fibres expressing P2X3 receptors in the myenteric plexus of rat stomach and coexistence of the P2X3 receptor with calbindin, calretinin and NOS during postnatal development, were investigated with immunostaining methods. Extrinsic nerves expressing P2X3 receptors appeared as early as E12 and were localised in the trunk and branches of the vagus nerve, which extended rapidly onto the whole rat stomach from E12 to E14. Intrinsic neurone cell bodies with P2X3-immunoreactivity in the myenteric ganglia were first demonstrated postnatally at P1, and at P14, when the number of neurones expressing the P2X3 receptor peaked at 45%. P2X3 receptor-immunoreactivity decreased subsequently, and at P60 only about 11% were P2X3-immunoreactive. Intraganglionic laminar nerve endings and intramuscular arrays were first demonstrated postnatally at P1 and P7, respectively. In the early postnatal days, there were many growth cone-like structures with strong P2X3 immunostaining associated with these endings and arrays. Double-immunostaining showed that 9–15% of P2X3-immunoreactive neurones in the gastric myenteric plexus expressed calbindin D-28 k only in the early postnatal days, while 14–21% of neurones from P1 to P60 increasingly expressed calretinin. About 20% of neurones with P2X3 immunoreactivity coexpressed NOS throughout perinatal development. 相似文献
7.
The understanding of how pain is processed at each stage in the peripheral and central nervous system is the precondition
to develop new therapies for the selective treatment of pain. In the periphery, ATP can be released from various cells as
a consequence of tissue injury or visceral distension and may stimulate the local nociceptors. The highly selective distribution
of P2X3 and P2X2/3 receptors within the nociceptive system has inspired a variety of approaches to elucidate the potential role of ATP as a
pain mediator. Depolarization by ATP of neurons in pain–relevant neuronal structures such as trigeminal ganglion, dorsal root
ganglion, and spinal cord dorsal horn neurons are well investigated. P2X receptor-mediated afferent activation appears to
have been implicated in visceral and neuropathic pain and even in migraine and cancer pain. This article reviews recently
published research describing the role that ATP and P2X receptors may play in pain perception, highlighting the importance
of the P2X3 receptor in different states of pain. 相似文献
8.
Seil M El Ouaaliti M Fontanils U Etxebarria IG Pochet S Dal Moro G Marino A Dehaye JP 《Purinergic signalling》2010,6(4):405-416
The response to ATP of peritoneal macrophages from wild-type (WT) and P2X7-invalidated (KO) mice was tested. Low concentrations (1–100 μM) of ATP transiently increased the intracellular concentration
of calcium ([Ca2+]i) in cells from both mice. The inhibition of the polyphosphoinositide-specific phospholipase C with U73122 inhibited this
response especially in WT mice suggesting that the responses coupled to P2Y receptors were potentiated by the expression of
P2X7 receptors. One millimolar ATP provoked a sustained increase in the [Ca2+]i only in WT mice. The response to 10 μM ATP was potentiated and prolonged by ivermectin in both mice. One millimolar ATP increased
the influx of extracellular calcium, decreased the intracellular concentration of potassium ([K+]i) and stimulated the secretion of interleukin-1β (IL-1β) only in cells from WT mice. Ten micromolar ATP in combination with
3 μM ivermectin reproduced these responses both in WT and KO mice. The secretion of IL-1β was also increased by nigericin
in WT mice and the secretory effect of a combination of ivermectin with ATP in KO mice was suppressed in a medium containing
a high concentration of potassium. In WT mice, 150 μM BzATP stimulated the uptake of YOPRO-1. Incubation of macrophages from
WT and KO mice with 10 μM ATP resulted in a small increase of YOPRO-1 uptake, which was potentiated by addition of 3 μM ivermectin.
The uptake of this dye was unaffected by pannexin-1 blockers. In conclusion, prolonged stimulation of P2X4 receptors by a combination of low concentrations of ATP plus ivermectin produced a sustained activation of the non-selective
cation channel coupled to this receptor. The ensuing variations of the [K+]i triggered the secretion of IL-1β. Pore formation was also triggered by activation of P2X4 receptors. Higher concentrations of ATP elicited similar responses after binding to P2X7 receptors. The expression of the P2X7 receptors was also coupled to a better response to P2Y receptors. 相似文献
9.
This study examined the effects of season-long exposure of Chinese pine (Pinus tabulaeformis) to elevated carbon dioxide (CO2) and/or ozone (O3) on indole-3-acetic acid (IAA) content, activities of IAA oxidase (IAAO) and peroxidase (POD) in needles. Trees grown in
open-top chambers (OTC) were exposed to control (ambient O3, 55 nmol mol−1 + ambient CO2, 350 μmol mol−1, CK), elevated CO2 (ambient O3 + high CO2, 700 μmol mol−1, EC) and elevated O3 (high O3, 80 ± 8 nmol mol−1 + ambient CO2, EO) OTCs from 1 June to 30 September. Plants grown in elevated CO2 OTC had a growth increase of axial shoot and needle length, compared to control, by 20% and 10% respectively, while the growth
in elevated O3 OTC was 43% and 7% less respectively, than control. An increase in IAA content and POD activity and decrease in IAAO activity
were observed in trees exposed to elevated CO2 concentration compared with control. Elevated O3 decreased IAA content and had no significant effect on IAAO activity, but significantly increased POD activity. When trees
pre-exposed to elevated CO2 were transferred to elevated O3 (EC–EO) or trees pre-exposed to elevated O3 were transferred to elevated CO2 (EO–EC), IAA content was lower while IAAO activity was higher than that transferred to CK (EC–CK or EO–CK), the change in
IAA content was also related to IAAO activity. The results indicated that IAAO and POD activities in Chinese pine needles
may be affected by the changes in the atmospheric environment, resulting in the change of IAA metabolism which in turn may
cause changes in Chinese pine’s growth.
An erratum to this article can be found at 相似文献
10.
Changes in P2X<Subscript>3</Subscript> purinoceptors in sensory ganglia of the mouse during embryonic and postnatal development 总被引:2,自引:2,他引:0
The expression of the P2X3 nucleotide receptor in embryonic day 14–18, postnatal day 1–14 and adult mouse sensory ganglia was examined using immunohistochemistry. Nearly all sensory neurons in dorsal root ganglia, trigeminal ganglia and nodose ganglia in embryos at embryonic day 14 expressed P2X3 receptors, but after birth there was a gradual decline to about 50% of neurons showing positive immunostaining for P2X3. In embryos there were only small neurons, while from postnatal day 7 both large and small neurons were present. Isolectin B4 (IB4)-positive neurons in dorsal, trigeminal and nodose ganglia did not appear until birth, but the numbers increased to about 50% by postnatal day 14 when a high proportion of IB4-positive neurons were also positively labelled for the P2X3 receptor. About 10% of neurons in dorsal, trigeminal and nodose ganglia were positive for calcitonin gene-related peptide in embryos, nearly all of which stained for P2X3 receptors. This increased postnatally to about 35–40% in adults, although only a few colocalised with P2X3 receptors. Neurofilament 200 was expressed in about 50% of neurons in trigeminal ganglia in the embryo, and this level persisted postnatally. All neurofilament 200-positive neurons stained for P2X3 in embryonic dorsal root ganglia, trigeminal ganglia and nodose ganglia, but by adulthood this was significantly reduced. The neurons that were positive for calbindin in embryonic dorsal, trigeminal and nodose ganglia showed colocalisation with P2X3 receptors, but few showed colocalisation postnatally. 相似文献
11.
Ravindra S. Telang Vinthiya Paramananthasivam Srdjan M. Vlajkovic David J. B. Munoz Gary D. Housley Peter R. Thorne 《Purinergic signalling》2010,6(2):263-272
Extracellular adenosine triphosphate (ATP) has profound effects on the cochlea, including an effect on the regulation of the
endocochlear potential (EP). Noise-induced release of ATP into the endolymph activates a shunt conductance mediated by P2X2 receptors in tissues lining the endolymphatic compartment, which reduces the EP and, consequentially, hearing sensitivity.
This may be a mechanism of adaptation or protection from high sound levels. As inaction of such a process could contribute
to hearing loss, this study examined whether the action of ATP on EP changes with age and noise exposure in the mouse. The
EP and the endolymphatic compartment resistance (CoPR) were measured in mice (CBA/CaJ) aged between 3 and 15 months. The EP
and CoPR declined slightly with age with an associated small, but significant, reduction in auditory brainstem response thresholds.
ATP (100–1,000 μM) microinjected into the endolymphatic compartment caused a dose-dependent decline in EP correlated to a
similar decrease in CoPR. This was blocked by pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate, consistent with a P2X2 receptor-mediated shunt conductance. There was no substantial difference in the ATP response with age. Noise exposure (octave-band
noise 80–100 decibels sound pressure level (dBSPL), 48 h) in young animals induced an upregulation of the P2X2 receptor expression in the organ of Corti and spiral limbus, most noticeably with the 90-dB exposure. This did not occur
in the aged animals except following exposure at 90 dBSPL. The EP response to ATP was muted in the noise-exposed aged animals
except following the 90-dB exposure. These findings provide some evidence that the adaptive response of the cochlea to noise
may be reduced in older animals, and it is speculated that this could increase their susceptibility to noise-induced injury. 相似文献
12.
Localisation of P2Y<Subscript>1</Subscript> and P2Y<Subscript>4</Subscript> receptors in dorsal root,nodose and trigeminal ganglia of the rat 总被引:5,自引:2,他引:3
The presence and distribution of P2Y (nucleotide) receptor subtypes in rat sensory neurons has been investigated. RT-PCR showed that P2Y1, P2Y2, P2Y4 and P2Y6 receptor mRNA is expressed in sensory ganglia [dorsal root ganglion (DRG), nodose ganglion (NG) and trigeminal ganglion (TG)]. The regional and cellular distribution of P2Y1 and P2Y4 receptor proteins in these ganglia was investigated using immunohistochemistry. P2Y1 polyclonal antibodies stained over 80% of the sensory neurons, particularly the small-diameter (neurofilament-negative) neurons. The P2Y4 receptor antibody stained more medium- and large- (neurofilament-positive) diameter neurons than small-diameter neurons. P2Y1 and P2Y4 receptor immunoreactivity (P2Y1-IR and P2Y4-IR) was often coexpressed with P2X3 receptor immunoreactivity (P2X3-IR) in subpopulations of neurons. Double immunohistochemistry showed that 73–84% of P2X3 receptor-positive neurons also stained for the P2Y1 receptor in DRG, TG and NG while only 25–35% also stained for the P2Y4 receptor. Subpopulations of P2Y1-IR neurons were coexpressed with NF200, CGRP and IB4; most P2Y4-IR neurons were coexpressed with NF200, while only a few neurons were coexpressed with CGRP (10–20%) or with IB4 (1–2%). The results suggest that P2Y as well as P2X receptor subtypes contribute to purinergic signalling in sensory ganglia. 相似文献
13.
Kumar A Singhal NK Ramanujam B Mitra A Rameshwaram NR Nadimpalli SK Rao CP 《Glycoconjugate journal》2009,26(4):495-510
Several C1-imino conjugates of d-galactose, d-lactose and d-ribose, where the nitrogen center was substituted by the salicylidene or naphthylidene, were synthesized and characterized.
Similar C2-imino conjugates of d-glucose have also been synthesized. All the glyco-imino-conjugates, which are transition state analogues, exhibited 100%
inhibition of the activity towards glycosidases extracted from soybean and jack bean meal. Among these, a galactosyl-napthyl-imine-conjugate
(1c) showed 50% inhibition of the activity of pure α-mannosidase from jack bean at 22 ± 2.5 μM, and a ribosyl-naphthyl-imine-conjugate
(3c) showed at 31 ± 5.5 μM and hence these conjugates are potent inhibitors of glycosidases. The kinetic studies suggested non-competitive
inhibition by these conjugates. The studies are also suggestive of the involvement of aromatic, imine and carbohydrate moieties
of the glyco-imino-conjugates in the effective inhibition. The binding of glyco-imino-conjugate has been established by extensive
studies carried out using fluorescence emission and isothermal titration calorimetry. The conformational changes resulted
in the enzyme upon interaction of these derivatives has been established by studying the fluorescence quench of the enzyme
by KI as well as from the secondary structural changes noticed in CD spectra. All these studies revealed the difference in
the binding strengths of the naphthylidene vs. salicylidene as well as galactosyl vs. lactosyl moieties present in these conjugates. The differential inhibition of these glyco-conjugates has been addressed by
quantifying the specific interactions present between the glyco-conjugates and the enzyme by using rigid docking studies.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
14.
Karawita R Senevirathne M Athukorala Y Affan A Lee YJ Kim SK Lee JB Jeon YJ 《Marine biotechnology (New York, N.Y.)》2007,9(4):479-490
The enzymatic extracts from seven species of microalgae (Pediastrum duplex, Dactylococcopsis fascicularis, Halochlorococcum porphyrae, Oltmannsiellopsis unicellularis, Achnanthes
longipes, Navicula sp. and Amphora coffeaeformis) collected from three habitats (freshwater, tidal pool, and coastal benthic) at Jeju Island in Korea were investigated for
their antioxidant activity. Of the extracts tested, the AMG 300 L (an exo 1, 4-α-d-glucosidase) extract of P. duplex, the Viscozyme extract of Navicula sp., and the Celluclast extract of A. longipes provided the most potential as antioxidants. Meanwhile, the Termamyl extract of P. duplex in an H2O2 scavenging assay exhibited an approximate 60% scavenging effect. In this study, we report that the DNA damage inhibitory
effects of P. duplex (Termamyl extract) and D. fascicularis (Kojizyme extract) were nearly 80% and 69% respectively at a concentration of 100 μg/ml. Thus, it is suggested that the microalgae
tested in this study yield promising DNA damage inhibitory properties on mouse lymphoma L 5178 cells that are treated with
H2O2. Therefore, microalgae such as P. duplex may be an excellent source of naturally occurring antioxidant compounds with potent DNA damage inhibition potential. 相似文献
15.
Inhibition of P2X<Subscript>7</Subscript> receptors by divalent cations: old action and new insight 总被引:1,自引:0,他引:1
Jiang LH 《European biophysics journal : EBJ》2009,38(3):339-346
16.
Although arsenic is an infamous carcinogen, it has been effectively used to treat acute promyelocytic leukemia, and can induce
cell cycle arrest or apoptosis in human solid tumors. Previously, we had demonstrated that opposing effects of ERK1/2 and
JNK on p21 expression in response to arsenic trioxide (As2O3) are mediated through the Sp1 responsive elements of the p21 promoter in A431 cells. Presently, we demonstrate that Sp1,
and c-Jun functionally cooperate to activate p21 promoter expression through Sp1 binding sites (−84/−64) by using DNA affinity
binding, chromatin immunoprecipitation, and promoter assays. Surprisingly, As2O3-induced c-Jun(Ser63/73) phosphorylation can recruit TGIF/HDAC1 to the Sp1 binding sites and then suppress p21 promoter activation.
We suggest that, after As2O3 treatment, the N-terminal domain of c-Jun phosphorylation by JNK recruits TGIF/HDAC1 to the Sp1 sites and then represses p21
expression. That is, TGIF is involved in As2O3-inhibited p21 expression, and then blocks the cell cycle arrest. 相似文献
17.
A theoretical study of a sandwich compound with a metal monolayer sheet between two aromatic ligands is presented. A full
geometry optimization of the [Au3Cl3Tr2]2+ (1) compound, which is a triangular gold(I) monolayer sheet capped by chlorines and bounded to two cycloheptatrienyl (Tr)
ligands was carried out using perturbation theory at the MP2 computational level and DFT. Compound (1) is in agreement with
the 18–electron rule, the bonding nature in the complex may be interpreted from the donation interaction coming from the Tr
rings to the Au array, and from the back-donation from the latter to the former. NICS calculations show a strong aromatic
character in the gold monolayer sheet and Tr ligands; calculations done with HOMA, also report the same aromatic behavior
on the cycloheptatrienyl fragments giving us an insight on the stability of (1). The Au –Au bond lengths indicate that an
intramolecular aurophilic interaction among the Au(I) cations plays an important role in the bonding of the central metal
sheet.
Figure (a) Ground state geometry of complex 1; (b) Top view of compound 1 and Wiberg bond orders computed with the MP2/B1 computational method; (c) Lateral view of compound 1 and NICS values calculated with the MP2/B1 method; the values in parenthesis were obtained at the VWN/TZP level 相似文献
18.
We investigated the contribution of L-, N- and P/Q-type Ca2+ channels to the [Ca2+]i changes, evoked by kainate, in the cell bodies of hippocampal neurons, using a pharmacological approach and Ca2+ imaging. Selective Ca2+ channel blockers, namely nitrendipine, ω-Conotoxin GVIA (ω-GVIA) and ω-Agatoxin IVA (ω-AgaIVA) were used. The [Ca2+]i changes evoked by kainate presented a high variability, and were abolished by NBQX, a AMPA/kainate receptor antagonist, but
the N-methyl-d-aspartate (NMDA) receptor antagonist, D-AP5, was without effect. Each Ca2+ channel blocker caused differential inhibitory effects on [Ca2+]i responses evoked by kainate. We grouped the neurons for each blocker in three subpopulations: (1) neurons with responses
below 60% of the control; (2) neurons with responses between 60% and 90% of the control, and (3) neurons with responses above
90% of the control. The inhibition caused by nitrendipine was higher than the inhibition caused by ω-GVIA or ω-AgaIVA. Thus,
in the presence of nitrendipine, the percentage of cells with responses below 60% of the control was 41%, whereas in the case
of ω-GVIA or ω-AgaIVA the values were 9 or 17%, respectively. The results indicate that hippocampal neurons differ in what
concerns their L-, N- and P/Q- type Ca2+ channels activated by stimulation of the AMPA/kainate receptors.
Special issue article in honor of Dr. Ricardo Tapia. 相似文献
19.
Systemic lupus erythematosus and its murine equivalent, modelled in the New Zealand Black and New Zealand White (NZB × NZW)F1 hybrid strain, are polygenic inflammatory diseases, probably reflecting an autoimmune response to debris from cells undergoing
programmed cell death. Several human and murine loci contributing to disease have been defined. The present study asks whether
the proinflammatory purinergic receptor P2X7, an initiator of a form of programmed cell death known as aponecrosis, is a candidate product of murine and human lupus susceptibility
loci. One such locus in (NZB × NZW)F1 mice is lbw3, which is situated at the distal end of NZW chromosome 5. We first assess whether NZB mice and NZW mice carry distinct alleles
of the P2RX
7 gene as expressed by common laboratory strains, which differ in sensitivity to ATP stimulation. We then compare the responses
of NZB lymphocytes, NZW lymphocytes and (NZB × NZW)F1 lymphocytes to P2X7 stimulation. NZB and NZW parental strains express the distinct P2X7-L and P2X7-P alleles of P2RX
7, respectively, while lymphocytes from these and (NZB × NZW)F1 mice differ markedly in their responses to P2X7 receptor stimulation. NZB mice and NZW mice express functionally distinct alleles of the proinflammatory receptor, P2X7. We show that current mapping suggests that murine and human P2RX
7 receptor genes lie within lupus susceptibility loci lbw3 and SLEB4, and we argue that these encode a product with the functional characteristics consistent with a role in lupus.
Furthermore, we argue that aponecrosis as induced by P2X7 is a cell death mechanism with characteristics that potentially have particular relevance to disease pathogenesis. 相似文献
20.
There is abundant evidence that extracellular ATP and other nucleotides have an important role in pain signaling at both the periphery and in the CNS. At first, it was thought that ATP was simply involved in acute pain, since ATP is released from damaged cells and excites directly primary sensory neurons by activating their receptors. However, neither blocking P2X/Y receptors pharmacologically nor suppressing the expression of P2X/Y receptors molecularly in sensory neurons or in the spinal cord had an effect on acute physiological pain. The focus of attention now is on the possibility that endogenous ATP and its receptor system might be activated in pathological pain states, particularly in neuropathic pain. Neuropathic pain is often a consequence of nerve injury through surgery, bone compression, diabetes or infection. This type of pain can be so severe that even light touching can be intensely painful; unfortunately, this state is generally resistant to currently available treatments. An important advance in our understanding of the mechanisms involved in neuropathic pain has been made by a recent work demonstrating the crucial role of ATP receptors (i.e., P2X3 and P2X4 receptors). In this review, we summarize the role of ATP receptors, particularly the P2X4 receptor, in neuropathic pain. The expression of P2X4 receptors in the spinal cord is enhanced in spinal microglia after peripheral nerve injury, and blocking pharmacologically and suppressing molecularly P2X4 receptors produce a reduction of the neuropathic pain behaviour. Understanding the key roles of ATP receptors including P2X4 receptors may lead to new strategies for the management of neuropathic pain. 相似文献