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51.
Daniel F. Legler Marcel Loetscher Simon A. Jones Clemens A. Dahinden Michel Arock Bernhard Moser 《European journal of immunology》1996,26(4):753-758
The proteolytic cleavage product of complement component 3, (C3a), like C4a and C5a, is a potent anaphylatoxin and induces the production of inflammatory mediators in phagocytes. Notably, mast cells respond to C3a with the release of vasoactive substances, including histamine. We have examined the function and receptor binding of C3a in a human leukemic mast cell line, HMC-1. Similar to chemoattractant agonists in leukocytes, C3a induced rapid cytosolic free calcium concentration increases in HMC-1 cells. EGTA did not diminish this response, indicating that mobilizable Ca2+ was from intracellular stores. Receptors for C3a in HMC-1 cells couple in part to Bordetella pertussis toxin-sensitive G-proteins and, therefore, appear to belong to the family of serpentine receptors that require G-proteins for signal transduction. HMC-1 cells express two types of C3a receptors, C3aR1 and C3aR2, that were shown to bind 125I-C3a with high-(Kd1 = 2.1–4.8 nM) or low-affinity (Kd2 = 30–150 nM), and both receptors are expressed at high level: 3 × 105–6 × 105 C3aR1/cell and 5 × 105–2.3 × 106 C3aR2/cell. Results from cross-linking experiments with 125I-C3a fully agree with the presence of two different classes of C3a receptors in HMC-1 cells. Two membrane proteins with apparent molecular masses of 54–61 kDa (p57) and 86–107 kDa (p97) could be covalently modified with 125I-C3a, and this cross-linking was inhibited with an excess of unlabeled C3a. Many of the known agonists for leukocytes including 13 chemokines (IL-8, NAP-2, GROα, ENA-78, IP10, PF4, MCP-1, 2 and 3, RANTES, MIP-1α, MIP-1β and 1309), three neuropeptides (neuropeptide Y, somatostatin and calcitonin), as well as C5a, did not activate HMC-1 cells, indicating that C3a is one of a few protein ligands for which this cell line expresses specific receptors. The apparent selectivity for C3a and the abundant expression of C3a receptors make the HMC-1 cell line an excellent choice for the cloning of the receptor genes. 相似文献
52.
Kyoko Hayashi 《Journal of medical virology》1995,47(4):323-329
Before completion of polarization, Madin-Darby canine kidney (MDCK) cells showed high infectivity and progeny production of herpes simplex virus type 1 infection. After polarization or formation of tight junctions, the infectivity and virus replication in MDCK cells was restricted significantly. The disruption of tight junctions by depletion of Ca2+ resulted in increasing virus infectivity and productivity. Mechanical disruption of tight junctions by scratching the cell monolayers with injection needle allowed markedly the replication of HSV-I in the cells aligned along the injured area. In polarized MDCK cells the progeny were released preferentially from the apical surface of the cells. These data suggest that because polarized MDCK cells mimic the epithelial cell layers, this cell line is helpful for determining the factors which regulate viral transmission in the human body. © Wiley-Liss, Inc. 相似文献
53.
Mechanical properties of isolated smooth muscle strips from human urinary bladder were investigated in vitro. Bladder tissue was obtained from tumour-free wall regions of bladders from male patients undergoing cystectomy for bladder carcinoma. In intact muscle strips, activated with high-K+ solution, half-maximal force occurred at about 0.9 mm extracellular [Ca2+]. The length-active force relation was determined and the muscle strips were fixed for light and electron microscopy at optimal length for active force (Io). The maximal active force per unit smooth muscle cross-sectional area was 208±49 mN/mm2, n= 6. Chemically skinned preparations were obtained by treatment with triton X-100. These preparations had a steep [Ca2+]-force relation in the micromolar range which was influenced by calmodulin. The skinned preparations could be maximally activated by irreversible thiophosphorylation of the regulatory light chains. The force-velocity relation was determined in the maximally activated skinned muscle at 22 °C at 0.5 1o. When the muscle was shortened by 10%, force was reduced by 35% whereas the maximal shortening velocity was little affected. 相似文献
54.
Chuen -Mao Yang Hui -Liang Tsao Chi -Tso Chiu Lir -Wan Fan Sheu -Meei Yu 《Pflügers Archiv : European journal of physiology》1996,432(4):708-716
The effects of increases in cellular adenosine 3′5′-cyclic monophosphate (cAMP) on 5-hydroxytryptamine-(5-HT-) induced generation
of inositol phosphates (IPs) and increases in intracellular Ca2+ ([Ca2+]i) were investigated using canine cultured tracheal smooth muscle cells (TSMCs). Cholera toxin and forskolin induced concentration-
and time-dependent cAMP formation with half-maximal effects (−logEC50) produced at concentrations of 7.0 ± 0.5 and 4.9 ± 0.4 respectively. Pretreatment of TSMCs with either forskolin or dibutyryl
cAMP inhibited 5-HT-stimulated responses. Even after treatment for 24h, these agents still inhibited the 5-HT-induced Ca2+ mobilization. The inhibitory effects of these agents produced both depression of the maximal response and a shift to the
right of the concentration response curves of 5-HT. The water-soluble forskolin analogue L-858051 [7-deacetyl-7β-(γ-N-methylpiperazino)-butyryl forskolin] significantly inhibited the 5-HT-stimulated accumulation of IPs. In contrast, the addition
of 1,9-dideoxy forskolin, an inactive forskolin analogue, had little effect on this response. Moreover, SQ-22536 [9-(tetrahydro-2-furanyl)-9-H-purin-6-amine], an inhibitor of adenylate cyclase, and both H-89 [N-(2-aminoethyl)-5-isoquinolinesulphonamide] and HA-1004[N-(2-guanidinoethyl)-5-isoquinolinesulphonamide], inhibitors of cAMP-dependent protein kinase (PKA), attenuated the ability
of forskolin to inhibit the 5-HT-stimulated accumulation of IPs. These results suggest that activation of cAMP/PKA was involved
in these inhibitory effects of forskolin. The AlF4
−-induced accumulation of IPs was inhibited by forskolin, suggesting that G protein(s) are directly activated by AlF4
−- and uncoupled from phospholipase C by forskolin treatment. These results suggest that activation of cAMP/PKA might inhibit
the 5-HT-stimulated phosphoinositide breakdown and consequently reduce the [Ca2+]i increase or inhibit both responses independently.
Received: 14 March 1996/Accepted: 10 April 1996 相似文献
55.
Sylviane Tardivel Lea Razanamaniraka Tilman Drüeke Bernard Lacour 《Pflügers Archiv : European journal of physiology》1995,429(4):470-476
The effect of sorbitol on Ca uptake by isolated ileal epithelial cells was investigated. Intestinal cells were isolated from rat ileum by mechanical vibration.45Ca uptake was approximately 2 times higher in cells exposed to 200 mM sorbitol ofd-alanine than in control cells. This enhancing effect of sorbitol on percentage Ca uptake decreased with increasing Ca concentrations in the incubation medium suggesting an effect on Ca entry velocity. The addition of 10 M nifedipine or 200 M verapamil to the incubation medium was devoid of any effect on Ca uptake in ileal cells, whereas 100 M trifluoperazine or chlorpromazine abolished the stimulatory effect of sorbitol. Finally, the effect of sorbitol on isolated cells was independent of a measurable change of cellular ATP content. In conclusion, the stimulatory effect of sorbitol on ileal Ca uptake is probably exerted through mechanisms other than an increase in intracellular ATP concentration. Sorbitol may enhance enterocyte Ca transport via a direct interaction with calmodulin and/or the Ca pump. It may also exert its effect through an inhibition of the basolateral Na Ca exchanger. 相似文献
56.
K.-M. Zhang Ping Hu Shang-Wu Wang Leon D. Wright Andrew S. Wechsler John A. Spratt F. N. Briggs 《Pflügers Archiv : European journal of physiology》1997,433(6):766-772
Using an immunohistochemical double-labeling technique, we observed that different isoforms of sarcoplasmic reticulum Ca-ATPase
are co-expressed in single fibers of canine fast-twitch skeletal muscles stimulated chronically at low frequency. By 7 days
of neuromuscular stimulation, the population of hybrid fibers expressing both SERCA1 and SERCA2a [fast- and slow-twitch isoforms
of sarco(endo)plasmic reticulum Ca2+-ATPase] had increased from 1.5% to 9.2% of fibers. By 14 days of stimulation 90% of the pure fast-twitch fibers (expressing
only SERCA1) were replaced by hybrid fibers. An additional 28 days of stimulation caused all fast-twitch fibers to express
SERCA2a at the same level as found in nonstimulated slow-twitch fibers (expressing only SERCA2a). At this time, one-half of
the previously hybrid fibers had become pure slow-twitch fibers. The remaining one-half of the hybrid fibers expressed SERCA1
at a very low level. Extending stimulation to 70 days did not further change the percentage of fibers that were slow-twitch
or hybrid. Immunoblot studies at the whole-muscle level confirmed that changes in SERCA expression at 42 days of neuromuscular
stimulation were complete. Immunohistochemical analysis of longitudinal sections of muscle showed that the changes in SERCA
protein were uniform along the length of the muscle fiber, indicating that nuclei along its length responded equally to chronic
stimulation.
Received: 12 November 1996 / Received after revision and accepted: 16 December 1996 相似文献
57.
H. Ochiai N. Hishiyama K. Higa K. Koyama M. Seita H. Fujise 《Comparative clinical pathology》2007,16(1):61-63
The cation transport and regulatory volume decrease (RVD) were investigated in the red blood cells (RBCs) of northern fur
seals (Callorhinus ursinus). Extracellular Ca-dependent Na efflux was increased to threefold by hypotonicity. K–Cl cotransport activity was not detected
by hypotonic medium, but measured only by nitrite or N-ethylmaleimide stimulation. RBCs were restored to their original volume after being swollen in hypoosmotic medium with Ca,
though this recovery was inhibited by the addition of quinidine. Based on these results, Na/Ca exchange transporter played
the major role in the regulatory volume decrease in the RBCs of northern fur seals.
H. Fujise has passed away. 相似文献
58.
Membrane currents of guinea-pig ventricular myocytes were recorded using the whole-cell voltage clamp method. The epinephrine-induced increase in Ca2+ current (2.9±0.5 times control) was reduced (1.8 ±0.3 times) by replacing Na+ with Li+ in the bathing solution. In addition, 0.5 M epinephrine increased a time-independent membrane conductance in the Na+ external solution, having a reversal potential of –19 ±3 mV (epinephrine-induced current). In the Li+ external solution, however, 0.5 M epinephrine failed to induce the epinephrine-induced current. The findings are consistent with the reported Li+ inhibition of GTP-binding protein and/or adenylate cyclase. 相似文献
59.
C. H. Orchard G. L. Smith D. S. Steele 《Pflügers Archiv : European journal of physiology》1998,435(4):555-563
Rat ventricular trabeculae were mounted for isometric tension recording, and then permeabilized with saponin. The Ca2+ concentration ([Ca2+]) within the permeabilized preparation (cytosolic [Ca2+]) was monitored continuously using Indo-1 and the integrals of Ca2+ transients resulting from brief caffeine application used as an index of the sarcoplasmic reticulum (SR) Ca2+ content. The relationship between SR Ca2+ content and cytosolic [Ca2+] was studied within the reported physiological range (i.e. 50–250 nmol · l–1 Ca2+). Increasing cytosolic [Ca2+] from 50 nmol · l–1 to 250 nmol · l–1 increased the steady-state SR Ca2+ content about threefold. However, increasing [Ca2+] above 250 nmol · l–1 typically resulted in spontaneous SR Ca2+ release, with no further increase in SR Ca2+ content. The SR Ca2+ content increased only slowly when cytosolic [Ca2+] was increased; it was unchanged 20 s after a rapid increase in cytosolic [Ca2+], but increased progressively to a new steady-state level during the following 1–2 min. In a parallel series of experiments
using intact papillary muscles, increasing extracellular [Ca2+] (from 0.5 to 5 mmol · l–1) significantly increased twitch tension within 20 s of the solution change. These results support previous suggestions that
the SR Ca2+ content may increase when diastolic cytosolic [Ca2+] rises during inotropic interventions such as increased stimulus rate or extracellular [Ca2+]. However, the rate at which SR Ca2+ responds to changes in cytoplasmic [Ca2+] within the diastolic range does not appear rapid enough to explain the early potentiation of twitch tension in intact preparations
after an increase in extracellular [Ca2+].
Received: 26 August 1997 / Accepted: 28 October 1997 相似文献
60.
目的:探讨失血性休克对大鼠肠系膜上动脉血管平滑肌BKCa通道酪氨酸磷酸化的影响以及NO对BKCa通道酪氨酸磷酸化的调控。方法:建立大鼠失血性休克模型[(35±5)mmHg]并提取肠系膜上动脉总裂解蛋白,采用免疫沉淀及免疫印迹技术,观察休克血管平滑肌BKCa通道酪氨酸磷酸化的变化情况;采用原代培养的大鼠肠系膜上动脉血管平滑肌细胞,观察NO对BKCa通道酪氨酸磷酸化的调控及其时-效、量-效关系。结果:失血性休克2 h及4 h后大鼠肠系膜上动脉血管平滑肌BKCa通道α亚基酪氨酸磷酸化明显增强 (P<0.01 );L-精氨酸(5×10-5-5×10-4 mol/L)孵育30 min即可诱导培养血管平滑肌细胞BKCa通道α亚基酪氨酸磷酸化增强,2 h内无明显下降;且L-精氨酸诱导BKCa通道α亚基酪氨酸磷酸化具有剂量依赖性。结论:重症失血性休克可增强血管平滑肌BKCa 通道酪氨酸磷酸化,且NO参与了该调控过程。 相似文献