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1.
The role of trans-sarcolemma membrane electron efflux in the α-adrenergic control of Ca2+ influx in perfused rat heart was examined. Electron efflux was measured by monitoring the rate of reduction of extracellular ferricyanide and compared with changes in contractility, as an indirect assessment of changes in cytoplasmic Ca2+ concentration. Methoxamine and phenylephrine each increased the rate of ferricyanide reduction from 80 to approx. 114 nmol/min per g wet wt. of heart, with half-maximal activation occurring at 10 μM for each agonist. Activation of the rate of ferricyanide reduction by both 10 μM methoxamine and 10 μM phenylephrine was blocked by the α-adrenergic antagonist, phenoxybenzamine, but not by the β-antagonist, propranolol. Stimulation of the rate of ferricyanide reduction by the α-agonist coincided with the increase in contractility, each reaching maximum values at approx. 80 s. Removal of the α-agonists led to parallel decreases in contractility and the rate of reduction, each returning to pre-stimulation values in approx. 400 s. In addition, the relationship between Ca2+ and ferricyanide reduction was examined. Perfusion of the heart with medium containing 6 mM CaCl2 significantly increased contractility and the rate of ferricyanide reduction. Perfusion of the heart with low Ca2+ diminished contractility, did not affect the rate of ferricyanide reduction, but amplified the stimulatory effect of methoxamine on this rate. The increase in ferricyanide reduction by α-adrenergic agonists resulted from a change in the apparent Vmax, indicative of an increase in electron efflux sites in the plasma membrane. It is concluded that α-adrenergic control of electron efflux closely parallels changes in contractility and therefore changes in the cytoplasmic concentration of Ca2+. The data suggest that α-agonist-mediated changes in electron efflux may lead to Ca2+ influx.  相似文献   

2.
M Endoh  S Motomura 《Life sciences》1979,25(9):759-768
In the isolated rabbit papillary muscle, experiments were carried out in order to elucidate whether or not cholinergic stimulation produces a differential antagonistic action on the positive inotropic effects mediated via β- and α-adrenoceptor stimulation. Carbachol (0.1–30 μM) alone scarcely affected the basal tension developed. The postive inotropic effects of phenylephrine (30 μM) in the presence of phentolamine and of isoprenaline, which were mediated via β-adrenoceptors, were markedly inhibited by carbachol. Carbachol (3 μM) shifted the dose-response curve for isoprenaline in a parallel manner, and that for phenylephrine with phentolamine to the right and downwards. Carbachol administered during induction of the positive inotropic effects via α-adrenoceptors by phenylephrine (30 μM) with pindolol or by methoxamine failed to inhibit these effects and increased further the tension developed. The dose-response curve for phenylephrine determined in the presence of pindolol was not affected by carbachol. The present results indicate that the cholinergic antagonism of the adrenergic action on the contractility of the mammalian ventricular myocardium is exerted specifically to the β-adrenoceptor-mediated action, but not to the α-adrenoceptor-mediated one.  相似文献   

3.
《Life sciences》1996,59(23):PL359-PL364
The effects of tetrandrine (TET) on the contractile responses of rat aortic rings and perfused rat mesenteric arteries to phenylephrine (PE) were investigated. TET inhibited the maximal contraction to PE in a concentration-dependent manner. TET significantly inhibited the transient contraction in Ca2+-free medium presumably due to release of intracellular Ca2+ after activation of α1-adrenoceptors. However, it caused a stronger inhibition of the sustained contraction in Ca2+-containing medium presumably the result of Ca2+ influx. TET has no inhibitory effect on caffeine-induced transient contraction. Radioligand receptor binding study using isolated dog aortic muscle membranes indicated that TET inhibited the binding of 3H-prazosin in a competitive manner, hence showing that TET interacted directly with the α1-adrenoceptors. Thus, TET affected PE-induced aortic contractions by multiple mechanisms, inhibiting interaction of PE with α1-adrenoceptors and interfering with PE-induced responses involving both Ca2+ entry and release.  相似文献   

4.
The study of erythrocytes of 80 men showed that adrenaline (10?10–10?6 g/mL) and phenylephrine (10?10–10?6 g/mL) dose-dependently increase the rate of agglutination of erythrocytes, judging by the decrease in the start time of agglutination, whereas ginipral (10?10–10?7 g/mL), on the contrary, decreases it. The effect of adrenaline and phenylephrine is blocked by nicergoline (10?6 g/mL), enhanced by obzidan (10?6 g/mL), and is not changed by yohimbine (10?6 g/mL) and atenolol (10?6 g/mL). These data indicate that the rate of agglutination increases with the activation of α1-adrenergic receptor (AR) and decreases with the activation of β2-AR, whereas the activation of α2- and β1-AR does not affect it. Trifluoperazine (10?6 g/mL) as a calmodulin antagonist, barium chloride (10?6 g/mL) as a Ca2+-dependent K+-channel blocker, and indomethacin (10?6 g/mL) as an inhibitor of cyclooxygenase and phospholipase A2 inhibit the ability of adrenaline to increase the rate of agglutination of erythrocytes. This suggests that this effect of adrenaline is caused by an increased Ca2+ entry into the erythrocyte, activation of calmodulin, cyclooxygenase, and phospholipase A2, and subsequent K+ release from the erythrocytes through the Ca2+-dependent K+ channels, which is regarded as a manifestation of eryptosis. Indirectly, this means that the potentiation of activation of α1-AR and β2-AR, respectively, increases and, conversely, decreases the rate of eryptosis.  相似文献   

5.
AimsThis study was designed to investigate the effects of sodium ferulate (SF) on rat isolated thoracic aortas and the possible mechanisms.Main methodsIsometric tension was recorded in response to drugs in organ bath. Cytosolic free Ca2+ concentration ([Ca2+]i) was measured using Fluo-3 in cultured rat aortic smooth muscle cells (RASMC).Key findingsSF (0.1–30 mM) relaxed the isolated aortic rings precontracted with phenylephrine (PE) and high-K+ in a concentration-dependent manner with respective pD2 of 2.7 ± 0.02 and 2.6 ± 0.06. Mechanical removal of endothelium did not significantly modify the SF-induced relaxation. In Ca2+-free solution, SF noticeably inhibited extracellular Ca2+-induced contraction in high-K+ and PE pre-challenged rings, and suppressed the transient contraction induced by PE and caffeine. The vasorelaxant effect of SF was unaffected by various K+ channel blockers such as tetraethylammonium, glibenclamide, 4-aminopyridine, and barium chloride. In addition, SF concentration-dependently reduced the contraction induced by phorbol-12-myristate-13-acetate, an activator of protein kinase C (PKC), in the absence of extracellular Ca2+, with the pD2 of 2.9 ± 0.03. In RASMC, SF had no effect on PE- or KCl-induced [Ca2+]i increase either in the presence or in the absence of external Ca2+.SignificanceThese results indicate that SF acts directly as a non-selective relaxant to vascular smooth muscle. The direct inhibition of the common pathway after [Ca2+]i increase may account for the SF-induced relaxation in Ca2+-dependent contraction, while the blockage of the PKC-mediated contractile mechanism is likely responsible for the SF-induced relaxation in Ca2+-independent contraction.  相似文献   

6.
Elevation of glucose induces transient inhibition of insulin release by lowering cytoplasmic Ca2+ ([Ca2+]i) below baseline in pancreatic β-cells. The period of [Ca2+]i decrease (phase 0) coincides with increased glucagon release and is therefore the starting point for antisynchronous pulses of insulin and glucagon. We now examine if activation of adrenergic α2A and muscarinic M3 receptors affects the initial [Ca2+]i response to increase of glucose from 3 to 20 mM in β-cells situated in mouse islets. In the absence of receptor stimulation the elevation of glucose lowered [Ca2+]i during 90–120 s followed by rise due to opening of voltage-dependent Ca2+ channels. The period of [Ca2+]i decrease was prolonged by activation of the α2A adrenergic receptors (1 μM epinephrine or 100 nM clonidine) and shortened by stimulation of the muscarinic M3 receptors (0.1 μM acetylcholine). The latter effect was mimicked by the Na/K pump inhibitor ouabain (10–100 μM). The results indicate that prolonged initial decrease (phase 0) is followed by slow [Ca2+]i rise and shorter decrease followed by fast rise. It is concluded that the period of initial decrease of [Ca2+]i regulates the subsequent β-cell response to glucose.  相似文献   

7.

Background

Nicotinic acetylcholine receptors (nAChR) have been identified on a variety of cells of the immune system and are generally considered to trigger anti-inflammatory events. In the present study, we determine the nAChR inventory of rat alveolar macrophages (AM), and investigate the cellular events evoked by stimulation with nicotine.

Methods

Rat AM were isolated freshly by bronchoalveolar lavage. The expression of nAChR subunits was analyzed by RT-PCR, immunohistochemistry, and Western blotting. To evaluate function of nAChR subunits, electrophysiological recordings and measurements of intracellular calcium concentration ([Ca2+]i) were conducted.

Results

Positive RT-PCR results were obtained for nAChR subunits α3, α5, α9, α10, β1, and β2, with most stable expression being noted for subunits α9, α10, β1, and β2. Notably, mRNA coding for subunit α7 which is proposed to convey the nicotinic anti-inflammatory response of macrophages from other sources than the lung was not detected. RT-PCR data were supported by immunohistochemistry on AM isolated by lavage, as well as in lung tissue sections and by Western blotting. Neither whole-cell patch clamp recordings nor measurements of [Ca2+]i revealed changes in membrane current in response to ACh and in [Ca2+]i in response to nicotine, respectively. However, nicotine (100 μM), given 2 min prior to ATP, significantly reduced the ATP-induced rise in [Ca2+]i by 30%. This effect was blocked by α-bungarotoxin and did not depend on the presence of extracellular calcium.

Conclusions

Rat AM are equipped with modulatory nAChR with properties distinct from ionotropic nAChR mediating synaptic transmission in the nervous system. Their stimulation with nicotine dampens ATP-induced Ca2+-release from intracellular stores. Thus, the present study identifies the first acute receptor-mediated nicotinic effect on AM with anti-inflammatory potential.  相似文献   

8.
Zebrafish, like other teleosts, display rapid skin color change in response to the background through sympathetic nerves. Here, the α- and β-adrenoceptors of melanophores were studied pharmacologically both in zebrafish embryo and adult scale. In vitro experiments on adult scale melanophores demonstrated that both α1- and α2-adrenoceptors are functional in melanosome aggregation, the α2 subtype being predominant. Most melanophores in zebrafish embryos were able to concentrate melanosomes to α2-adrenergic agonist α-methylnorepinephrine when they first appeared. This ability increased at least in the following 48 h, showing melanophores at these stages have developed functional adrenoceptors and these receptors increase independently before sympathetic innervation. However, even high concentration (10−3 M) of α1-adrenoceptor agonist phenylephrine was not able to evoke any paling of the embryos. In adult scales, propranolol enhanced the melanosome-aggregating response of epinephrine and isoproterenol, but not norepinephrine, indicating β-adrenoceptor mediates melanosome-dispersing response in adult zebrafish. Similar response was not observed in embryos until 60 h post-fertilization (hpf). The melanophore adrenoceptor blocking effects of phentolamine and propranolol in embryos were much lower than that in adult zebrafish, suggesting these adrenoceptors in developing melanophores are less sensitive to the classical antagonists.  相似文献   

9.
Intracellular Ca2+ and cAMP typically cause opposing effects on airway smooth muscle contraction. Receptors that stimulate these pathways are therapeutic targets in asthma and chronic obstructive pulmonary disease. However, the interactions between different G protein-coupled receptors (GPCRs) that evoke cAMP and Ca2+ signals in human bronchial airway smooth muscle cells (hBASMCs) are poorly understood. We measured Ca2+ signals in cultures of fluo-4-loaded hBASMCs alongside measurements of intracellular cAMP using mass spectrometry or [3H]-adenine labeling. Interactions between the signaling pathways were examined using selective ligands of GPCRs, and inhibitors of Ca2+ and cAMP signaling pathways. Histamine stimulated Ca2+ release through inositol 1,4,5-trisphosphate (IP3) receptors in hBASMCs. β2-adrenoceptors, through cAMP and protein kinase A (PKA), substantially inhibited histamine-evoked Ca2+ signals. Responses to other Ca2+-mobilizing stimuli were unaffected by cAMP (carbachol and bradykinin) or minimally affected (lysophosphatidic acid). Prostaglandin E2 (PGE2), through EP2 and EP4 receptors, stimulated formation of cAMP and inhibited histamine-evoked Ca2+ signals. There was no consistent relationship between the inhibition of Ca2+ signals and the amounts of intracellular cAMP produced by different stimuli. We conclude that β-adrenoceptors, EP2 and EP4 receptors, through cAMP and PKA, selectively inhibit Ca2+ signals evoked by histamine in hBASMCs, suggesting that PKA inhibits an early step in H1 receptor signaling. Local delivery of cAMP within hyperactive signaling junctions mediates the inhibition.  相似文献   

10.
AimsThe goal of this study was to evaluate the influence of γ-irradiation on Ca2+-activated K+ channel (BKCa) function and expression in rat thoracic aorta.Main methodsAortic cells or tissues were studied by the measurement of force versus [Ca2+]i, patch-clamp technique, and RT-PCR.Key findingsStimulation of smooth muscle cells with depolarizing voltage steps showed expression of outward K+ currents. Paxilline, an inhibitor of BKCa channels, decreased outward K+ current density. Outward currents in smooth muscle cells obtained from irradiated animals 9 and 30 days following radiation exposure demonstrated a significant decrease in K+ current density. Paxilline decreased K+ current in cells obtained 9 days, but was without effect 30 days after irradiation suggesting the absence of BKCa channels. Aortic tissue from irradiated animals showed progressively enhanced contractile responses to phenylephrine in the post-irradiation period of 9 and 30 days. The concomitant Ca2+ transients were significantly smaller, as compared to tissues from control animals, 9 days following irradiation but were increased above control levels 30 days following irradiation. Irradiation produced a decrease in BKCa α- and β1-subunit mRNA levels in aortic smooth muscle cells suggesting that the vasorelaxant effect of these channels may be diminished.SignificanceThese results suggest that the enhanced contractility of vascular tissue from animals exposed to radiation may result from an increase in myofilament Ca2+ sensitivity in the early post-irradiation period and a decrease in BKCa channel expression in the late post-irradiation period.  相似文献   

11.
The dependence of chloride permeability of the human sweat gland cell line NCL-SG3 cell line on cytosolic free calcium ([Ca2+]i) was investigated. X-ray microanalysis, fura-2 fluorescence and patch clamp methodology were used. Carbachol and A23187 decreased cellular Cl and K for cells grown on permeable supports, but carbachol had no effect on cells grown on impermeable supports. In perforated patch experiments with impermeable supports, ATP and calcium ionophores increased the inward current (ic) whereas carbachol had no effect. ic was unaffected by cation channel blockers or removal of extracellular Na+ but was blocked by chloride channel blockers. Lowering bath Ca2+ decreased ic. On raising bath Ca2+ ic and [Ca2+]i responded with a transient rise which was not blocked by La3+ or D-600. La3+, but not D-600, blocked the entry of Mn2+. K+-depolarization and Bay-K-8644 had little effect on [Ca2+]i. The rise in [Ca2+]i may be mediated primarily via depletion operated Ca2+-channels. Irrespective of substrate NCL-SG3 cells have a chloride permeability which depends on [Ca2+]i.  相似文献   

12.
《Life sciences》1993,52(16):PL135-PL139
β-Adrenoceptors are present on vascular smooth muscle and on endothelium. We investigated whether the endothelial β-adrenoceptors induce relaxation of rat mesentric resistance arteries by stimulation of endothelium-derived relaxing factor (EDRF) release. To this end, the relaxation was studied in the presence and absence of 100 μM NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of the production of EDRF. The maximal relaxation with isoprenaline, expressed as a percentage of the precontraction, was 44.0 ± 4.0 % (n = 12) in the L-NMMA treated group and 58.0 ± 2.6 % (n = 13) in the untreated group, a statistically significant difference (P = 0.008). However, the precontraction with 40 mM K+ tended to be higher in the presence of L-NMMA. The pD2-value for isoprenaline was not significantly changed by the L-NMMA treatment. We conclude that the isoprenaline-mediated relaxation of mesenteric resistance arteries in inhibited by L-NMMA, bu that this effect can at least in part be ascribed to an inhibition of baseline EDRF-release.  相似文献   

13.
Abstract— ATP-induced changes in the intracellular Ca2+concentration ([Ca2+]i) in neuroblastoma glioma hybrid NG108–15 cells were studied. Using the fluorescent Ca2+indicator fura-2, we have shown that the [Ca2+]i increased in response to ATP. ATP at 3 mM caused the greatest increase in [Caz+]i, whereas at higher concentrations of ATP the response became smaller. Two nonhydrolyzable ATP analogues, adenosine 5′-thiotriphosphate and 5′-adenylyl-β, γ-imidodiphosphate, could not trigger significant [Ca2+]i change, but they could block the ATP effect. Other adenine nucleotides, including ADP, AMP, α,β-methylene-ATP, β,γ-methylene-ATP, and 2-methylthio-ATP, as well as UTP and adenosine, all had no effect on [Ca2+]i at 3 mM. In the absence of extracellular Ca2+, the effect of ATP was inhibited totally, but could be restored by the addition of Ca2+ to the cells. Upon removal of Mg2+, the maximum increase in [Ca2+]i induced by ATP was enhanced by about 42%. Ca2+-channel blockers partially inhibited the ATP-induced [Ca2+]i rise. The ATP-induced [Ca2+]i rise was not affected by thapsigargin pretreatment, though such pretreatment blocked bradykinin-induced [Ca2+]i rise completely. No heterologous desensitization of [Ca2+]i rise was observed between ATP and bradykinin. The magnitude of the [Ca2+]i rise induced by ATP increased between 1.5 and 3.1 times when external Na+was replaced with Tris, N-methyl-d -glucamine, choline, or Li+. The addition of EGTA or verapamil to cells after their maximum response to ATP immediately lowered the [Ca2+]i to the basal level in Na+-containing or Na+-free Tris solution. Our results suggest that ATP stimulates Ca2+influx via at least two pathways: ion channels that are permeable to Ca2+ and Na+, and pores formed by ATP4-.  相似文献   

14.
Hepatocytes isolated from the livers of fed rats were used for a comparative study of the effects of phenylephrine, vasopressin and glucagon on gluconeogenesis and on enzymes of glycogen metabolism. When hepatocytes were incubated in the presence of Ca2+, phenylephrine stimulated gluconeogenesis from pyruvate less than did glucagon, but, in contrast with this hormone, it did not affect the activities of protein kinase and pyruvate kinase, nor the concentration of phosphoenolpyruvate, and it did not decrease the release of 3H2O from [6-3H]glucose. The effects of vasopressin were similar to those of phenylephrine. Gluconeogenesis from fructose was also stimulated by phenylephrine and, more markedly, by glucagon at the expense of the conversion of fructose into lactate. Insulin was able to antagonize the stimulatory effect of phenylephrine on gluconeogenesis from pyruvate. When Ca2+ was removed from the incubation medium, phenylephrine still stimulated gluconeogenesis from pyruvate, but it also caused an activation of protein kinase and an inactivation of pyruvate kinase; accordingly, the concentration of phosphoenolpyruvate was increased, and, in contrast, vasopressin had no effect on all these parameters. The property of phenylephrine to cause the activation of glycogen phosphorylase was decreased by glucose or by the absence of Ca2+; it was abolished when these two conditions were combined. Glycogen synthase was inactivated by phenylephrine in the presence or the absence of Ca2+, although presumably by different mechanisms.  相似文献   

15.
We studied the effects of increased Ca2+ influx on α1‐adrenoceptor‐stimulated InsP formation in adult rat cardiac myocytes. We further examined if such effects could be mediated through a specific α1‐adrenoceptor subtype. [3H]InsP responses to adrenaline were dependent on extracellular Ca2+ concentration, from 0.1 μM to 2 mM, and were completely blocked by Ca2+ removal. However, in cardiac myocytes preloaded with BAPTA, a highly selective calcium chelating agent, Ca2+ concentrations higher than 1 μM had no effect on adrenaline‐stimulated [3H]InsP formation. Taken together these results suggest that [3H]InsP formation induced by α1‐adrenergic stimulation is in part mediated by increased Ca2+ influx. Consistent with this, ionomycin, a calcium ionophore, stimulated [3H]InsP formation. This response was additive with the response to adrenaline stimulation implying that different signaling mechanisms may be involved. In cardiac myocytes treated with the α1B‐adrenoceptor alkylating agent, CEC, [3H]InsP formation remained unaffected by increased Ca2+ concentrations, a pattern similar to that observed when intracellular Ca2+ was chelated with BAPTA. In contrast, addition of the α1A‐subtype antagonist, 5′‐methyl urapidil, did not affect the Ca2+ dependence of [3H]InsP formation. Neither nifedipine, a voltage‐dependent Ca2+ channel blocker nor the inorganic Ca2+ channel blockers, Ni2+ and Co2+, had any effect on adrenaline stimulated [3H]InsP, at concentrations that inhibit Ca2+ channels. The results suggest that in adult rat cardiac myocytes, in addition to G protein‐mediated response, α1‐adrenergic‐stimulated [3H]InsP formation is activated by increased Ca2+ influx mediated by the α1B‐subtype. J. Cell. Biochem. 84: 201–210, 2002. © 2001 Wiley‐Liss, Inc.  相似文献   

16.
The effect of somatostatin (SRIF) on norepinephrine (NE) release from the brain tissue was determined on the superfused rat cerebral cortex slices preloaded with 3HNE. SRIF (0.38 μM–1.53 μM) was found to stimulate dose-dependently tritium (3H) overflow evoked electrically by 30%—116% although SRIF did not affect on the spontaneous 3H overflow. SRIF at the concentrations which exhibited the stimulatory effect inhibited scarecely the uptake of 3HNE by cortex slices, while the reference drug, cocaine (50 μM, 10 μM) markedly depressed the uptake. The stimulatory effect of SRIF was not reduced by phentolamine (3.14 μM), α-adrenoceptor blocker, which increased the evoked 3H overflow from the slices itself. These results suggest that SRIF does not produce its stimulatory effect by inhibiting the NE reuptake mechanisms or by interacting with the presynaptic α-adrenoceptors. Elevating of Ca2+ concentrations from 0.75 mM to 2.25 mM in the superfusion fluid reduced the stimulatory effect of SRIF. It is possible that SRIF stimulates NE release by facilitating the availability of Ca2+ for the release mechanisms.  相似文献   

17.
Conformational transitions of calmodulin as studied by vacuum-uv CD   总被引:1,自引:0,他引:1  
CD measurements were made for calmodulin and its calcium (Ca2+) complexes at different ionic strengths and Ca2+ concentrations. Calmodulin at an ionic strength of 0.00M and in the absence of Ca2+ exists as an α-helical protein with a negligible amount of β-sheet. An increase in ionic strength, whether or not Ca2+ is present, increases α-helix at the expense of “other” (coil) structure. The changes in β-sheet and β-turns are insignificant. Binding of Ca2+ at low ionic strength occurs in stages with at least one folding intermediate before attaining the final stable state. Binding of Ca2+ at an ionic strength of 0.165M causes only a slight increase in α-helix, so that the secondary structure of the protein depends on ionic strength and is insensitive to the nature of the cation (i.e., Ca2+). Thus, the activation of calmodulin by Ca2+ must be due to a structural reorientation rather than to a major secondary structural alteration. The CD estimation of secondary structure with 4 mol Ca2+/calmodulin (61% α-helix, 2% antiparallel β-sheet, 2% parallel β-sheet, 21% β-turns, and 14% other) is in excellent agreement with the x-ray results.  相似文献   

18.
19.
Beta-1 integrins have essential functions in hemopoietic and immune systems by controlling phenomenons such as cell homing and cell activation. The function α4β1 and α5β1 integrins is regulated by divalent cations and, as demonstrated more recently, by mitogenic cytokines which activate them by “inside-out” mechanisms. Using the adhesive interaction of a cytokine-dependent human hemopoietic cell line to immobilized fibronectin, we have analyzed the requirements in divalent cations Mn2+, Mg2+ and Ca2+ for α4β1 and α5β1 activation by “inside-out” mechanisms triggered by cytokines such as granulocyte-macrophage colony stimulating factor or KIT ligand, or by external conformational constraints with the function-activating anti-β1 integrin monoclonal antibody 8A2. The intrinsic difference between these two modes of β1 integrin activation was revealed by their different requirements in divalent cations. We found that in the absence of any divalent cations, α4β1 and α5β1 were non-functional even after further stimulation by cytokines or 8A2. However, whilst either Ca2+, Mg2+ or Mn2+ were able to restore adhesive functions of α4β1 and α5β1 when activated by 8A2, only Mg2+ and Mn2+ were able to support activation of α5β1 and α5β1 by cytokines. Furthermore, high concentrations of Ca2+ exceeding 20 mM dramatically inhibited cell adhesion to fibronectin induced by Mn2+ and cytokines but not by 8A2. On the contrary, in the presence of both Ca2+ and Mg2+, Mn2+ had an additive effect on the activation of α5β1 and α5β1 by mitogenic cytokines. The presence of the absence of these divalent cations did not inhibit early tyrosine phosphorylation induced by the binding of KIT ligand to its tyrosine-kinase receptor KIT. Therefore, we propose that in hemopoietic cells, Ca2+, Mg2+ and Mn2+ may modulate in vivo α4β1 and α5β1 regulation by mitogenic cytokines, a phenomenon involved in the regulation of hemopoietic progenitor cell homing within the bone marrow.  相似文献   

20.
《Life sciences》1994,56(5):PL103-PL108
We studied the effects of the aminosteroid U-73122, a putative phospholipase C (PLC) inhibitor, on carbachol-induced increases in insulin release, [Ca2+]i, and IP3 in β-TC3 cells. Carbachol (0.1–100 μM) increased [Ca2+]i and carbachol (0.1–1000 μM) increased insulin release dose-dependently. Carbachol (100 μM) also increased inositol 1,4,5-trisphosphate (IP3) production. U-73122 (2–12 νM) inhibited the effects of carbachol on [Ca2+]i and insulin release in a dose-dependent manner, and at the highest dose studied (12 μM) it abolished or greatly attenuated all three effects of carbachol. In contrast, U-73343 (12 μM), the analog of U-73122 that does not inhibit PLC, only inhibited the effect of carbachol on [Ca2+]i by 20% and did not inhibit the effect of carbachol on insulin release. Since carbachol increased IP3, [Ca2+]i, and insulin release by activating PLC, these results suggested that U-73122 inhibits phospholipase C-depenent processes in β-TC3 cells.  相似文献   

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