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At least 865 records · Page 48Linked to original sources
PubMed1999

Calcium and ATP regulation of ion transport in larval frog skin.

Ion transport measured as short circuit current (Isc) across the skin of larval frogs is activated by amiloride, acetylcholine, and ATP. In many epithelia, ATP stimulation of Isc involves an increase in intracellular calcium. To define the role of changes in intracellular calcium in ATP stimulation of Isc in larval frog skin, epithelial cells were loaded with calcium by adding 5 microM ionomycin to a 2 mM calcium apical Ringer's solution. Calcium loading had no observable effect on baseline Isc or on stimulation by ATP. Minimizing changes in intracellular calcium by loading the cell with the calcium chelator BAPTA also had no measurable effect on ATP stimulation of Isc. When the apical side was bathed with Ca(2+)-free Ringer's solution, ionomycin increased Isc up to 15 microA. This increase was partially blocked by 2 mM Ca2+, 2 mM Mg2+, and 10 microM W-7. Other experiments showed that baseline-stimulated and ATP-stimulated Isc were always larger in 2 mM Mg2+ Ringer's compared to 2 mM Ca2+. In dissociated cells bathed in 2 mM Ca2+ Ringer's, ATP had no effect on intracellular calcium as measured by Fluo-LR fluorescence changes. In conclusion, ATP apparently stimulates Isc without concomitant changes in intracellular calcium. This is consistent with a directly ligand-gated receptor at the apical membrane with P2X-like characteristics.

Adenosine Triphosphate↗
PubMed2005

Regulation of ion transport via apical purinergic receptors in intact rabbit airway epithelium.

We investigated purinergic receptors involved in ion transport regulation in the intact rabbit nasal airway epithelium. Stimulation of apical membrane P2Y receptors with ATP or UTP (200 microM) induced transient increases in short-circuit current (Isc) of 13 and 6% followed by sustained inhibitions to 8 and 17% below control level, respectively. Serosal application of nucleotides had no effect. The ATP-induced response appeared to involve additional activation of apical adenosine (P1) and P2X receptors. The inhibitory effect of ATP and UTP on Isc was eliminated by pretreatment with amiloride (100 microM), while the stimulatory effect was potentiated, indicating that ATP and UTP inhibit Na+ and stimulate Cl- current. Ionomycin (1 microM) induced responses similar to UTP and ATP and desensitized the epithelium to the nucleotides, indicating involvement of intracellular Ca2+ (Ca2+ i. Furthermore, ATP, UTP and ionomycin induced 21, 24, and 21% decreases, respectively, in transepithelial conductance. Measurements of unidirectional isotope fluxes showed a 39% decrease in the dominant net Na+ absorption in response to ATP, while the smaller net Cl- secretion increased only insignificantly and unidirectional Cl- fluxes decreased significantly. The results suggest that nucleotides released to the airway surface liquid exert an autocrine regulation of epithelial NaCl absorption mainly by inhibiting the amiloride-sensitive epithelial Na+ channel (ENaC) and paracellular anion conductance via a P2Y receptor-dependent increase in Ca2+ i, while stimulation of Cl- secretion is of minor importance.

Adenosine↗
PubMed2001

Large-conductance calcium-activated potassium channels in neonatal rat intracardiac ganglion neurons.

The properties of single Ca2+-activated K+ (BK) channels in neonatal rat intracardiac neurons were investigated using the patch-clamp recording technique. In symmetrical 140 mM K+, the single-channel slope conductance was linear in the voltage range -60/+60 mV, and was 207+/-19 pS. Na+ ions were not measurably permeant through the open channel. Channel activity increased with the cytoplasmic free Ca2+ concentration ([Ca2+]i) with a Hill plot giving a half-saturating [Ca2+] (K0.5) of 1.35 microM and slope of approximately equals 3. The BK channel was inhibited reversibly by external tetraethylammonium (TEA) ions, charybdotoxin, and quinine and was resistant to block by 4-aminopyridine and apamin. Ionomycin (1-10 microM) increased BK channel activity in the cell-attached recording configuration. The resting activity was consistent with a [Ca2+]i <100 nM and the increased channel activity evoked by ionomycin was consistent with a rise in [Ca2+]i to > or =0.3 microM. TEA (0.2-1 mM) increased the action potential duration approximately equals 1.5-fold and reduced the amplitude and duration of the afterhyperpolarization (AHP) by 26%. Charybdotoxin (100 nM) did not significantly alter the action potential duration or AHP amplitude but reduced the AHP duration by approximately equals 40%. Taken together, these data indicate that BK channel activation contributes to the action potential and AHP duration in rat intracardiac neurons.

Action Potentials↗
PubMed1998

Interleukin-10 expression is induced by increase of intracellular calcium levels in the monocytic cell line U937.

The regulation of interleukin-10 (IL-10) expression after treatment with a high, exponential, electric pulse was investigated in the monocytic cell line U937. Recently, we showed IL-10 protein production in the monocytic cell lines U937 and THP-1 after exposure to a single, high exponential electric pulse [Lehmann MH, Höffken K, Berg H (1996) Bioelectrochem. Bioenerg. 41: 227-229]. In the present study, the specificity of this process was proven by semiquantitative reverse-transcriptase polymerase chain reaction. It was found that the presence of calcium in the culture medium during the pulse is essential for IL-10 protein production. Only a small amount of IL-10 protein was produced in calcium free medium. The calcium specific chelator EGTA prevented IL-10 protein production induced by the electric pulse in a dose-dependent manner. Additionally, IL-10 mRNA transcription could be induced in U937 cells without pulse application by means of the calcium ionophore ionomycin. No IL-10 protein could be detected by ELISA. However, down-regulation of TNF-alpha mRNA levels after ionomycin stimulation provided an indirect proof that IL-10 protein production occurred.

Calcium↗
PubMed2006

Halotolerance is enhanced in carrot callus by sensing hypergravity: influence of calcium modulators and cytochalasin D.

Carrot callus was centrifuged at 10 g and compared to callus growing at 1 g on agar in the presence of increasing sodium chloride concentrations. Growth after 14 days was enhanced in the centrifuged samples versus samples kept at 1 g. This effect was not found when the samples were grown on potassium chloride. At 50 mM NaCl, the calcium ionophore ionomycin was applied to centrifuged and noncentrifuged callus samples. In both experiments, the growth of callus increased with increasing ionomycin concentrations but under 10 g this increase was more enhanced. As inhibitors of calcium influx, lanthanum and gadolinium chloride were chosen in the presence of 50 mM NaCl. Both inhibitors inhibited growth at 1 g at low concentrations of around 2 microM, whereas the centrifuged samples were not or much less so inhibited. We tested an involvement of actin by application of cytochalasin D to callus grown in the presence of 50 mM NaCl. In both types of samples, growth at 1 g and growth at 10 g, cytochalasin D enhanced growth but the effect was clearly stronger at 10 g than at 1 g. As increased halotolerance was only observed in the presence of increased sodium ions, not potassium ions, and as halotolerance is known to be induced by an influx of calcium, the data suggest that a calcium influx induced by hypergravity and possibly modulated by actin caused the observed increase in halotolerance at 10 g.

Actin Cytoskeleton↗
PubMed1993

Actions of interleukin-4 on prostaglandin biosynthesis at the chorion-decidual interface.

OBJECTIVE: We determined the effects of interleukin-4 on chorion and decidual prostaglandin production. STUDY DESIGN: Chorion and decidual cells from term placentas were grown to confluence. Cells were then incubated with interleukin-4 either alone or with other known stimulants of prostaglandin production: interleukin-1 beta, epidermal growth factor, ionomycin, or phorbol 12-myristate 13-acetate. Prostaglandin E2 production was determined with a specific radioimmunoassay. RESULTS: Interleukin-4 alone stimulated prostaglandin E2 production in chorion and decidual cells. Interleukin-4 significantly enhanced the stimulatory actions of phorbol 12-myristate 13-acetate, ionomycin, and epidermal growth factor but not interleukin-1 beta on prostaglandin E2 production. CONCLUSION: Interleukin-4 stimulates prostaglandin E2 production by chorion and decidual cells. These data suggest that interleukin-4 production by immune effector cells in gestational tissues may contribute to the pathophysiologic features of preterm labor.

Cells, Cultured↗
PubMed1994

Dynamic role of microfilaments in intestinal chloride secretion.

The importance of microfilaments in the regulation of chloride (Cl-) secretion by the human intestinal cell line T84 was investigated using the cytoskeletal probe phalloidin to bind and stabilize F-actin. Phalloidin was found to inhibit secretion mediated by cyclic adenosine monophosphate (cAMP) and the sustained secretory response to the calcium (Ca+2) ionophore ionomycin but not to affect the transient Ca+2-mediated response to carbachol and histamine. Fluorescent microscopic examination of F-actin revealed regionally restricted microfilament remodeling in cAMP- and ionomycin-treated cells. Normal regulation of apical Cl- and basolateral potassium (K+) channel functions was evident in phalloidin-loaded cells. It is concluded that prevention of cytoskeletal remodeling by actin stabilization inhibits the generation of a sustained Cl- secretory response by a mechanism that does not involve Cl- or K+ channels. Depolymerization of F-actin plays an integral role in the regulation of intestinal Cl- secretion.

Actin Cytoskeleton↗
PubMed1988

Phorbol myristate acetate potentiates superoxide release and membrane depolarization without affecting an increase in cytoplasmic free calcium in human granulocytes stimulated by the chemotactic peptide, lectins and the calcium ionophore.

We investigated the inter-relationships of superoxide (O2-) release, membrane depolarization and an increase in cytoplasmic free Ca2+, [Ca2+]i, in human granulocytes stimulated by various agonists. When concanavalin A or the Ca2+ ionophore ionomycin was used as stimulus, an increase in [Ca2+]i clearly preceded the onset of membrane depolarization, which was followed by O2- release. On the other hand, when N-formylmethionylleucylphenylalanine or wheat-germ agglutinin was used as stimulus, no demonstrable lag was seen in any of the responses. O2- release and membrane depolarization stimulated by all these agonists were markedly potentiated in parallel by pretreatment of cells with a low concentration of phorbol myristate acetate (0.25 ng/ml), whereas an increase in [Ca2+]i was not affected or minimally potentiated. The lag time between addition of the stimulus (concanavalin A or ionomycin) and onset of membrane depolarization or O2- release was significantly reduced by pretreatment of cells with phorbol myristate acetate, whereas the lag time between addition of concanavalin A and onset of the increase in [Ca2+]i was not affected. The dose-response curves for triggering of O2- release and membrane depolarization by each of receptor-mediated agonists in phorbol myristate acetate-pretreated or control cells were identical. These findings suggest that; (a) an increase in [Ca2+]i stimulates membrane depolarization indirectly; (b) a low concentration of phorbol myristate acetate potentiates membrane depolarization and O2- release by acting primarily at the post-receptor level, in particular, at the level distal to an increase in [Ca2+]i, but not by augmenting an increase in [Ca2+]i; and (c) the system provoking membrane depolarization and the system activating NADPH oxidase share a common pathway, which may be susceptible to a low concentration of phorbol myristate acetate.

Calcium↗
PubMed1989

Effects of sodium removal on calcium mobilization and dense granule secretion induced by thrombin in human platelets.

Removal of extracellular sodium decreased calcium mobilization from intracellular stores induced by thrombin in aspirin-treated human platelets. ATP and serotonin secretion were also significantly reduced. Secretion was positively correlated with calcium mobilization, but the presence or absence of sodium did not modify the slope of the regression line. Half-maximal secretion was reached when [Ca2+]i was increased by about 0.1 microM. Calcium mobilization induced by the divalent cation ionophore ionomycin was not modified by sodium removal. Secretion induced by ionomycin was much smaller than the thrombin-induced one for the same increases of [Ca2+]i. These results suggest that the presence of external sodium is required for normal thrombin-induced calcium release from the intracellular stores and hence for dense granule secretion. However, secretion cannot be only attributed to the increase of cell [Ca2+]i but also to other process(es) which are not affected by external sodium.

Adenosine Triphosphate↗
PubMed1990

Polarized 86Rb+ effluxes in primary cultures of rabbit kidney proximal cells: role of calcium and hypotonicity.

Isolated proximal cells from rabbit kidney were seeded on collagen-coated permeable supports. After 8 days, the cultured cells became organized as a confluent monolayer. The proximal origin of the monolayer was confirmed by enzymatic, immunological, electrical and electron microscopical studies. The epithelia exhibited a morphological polarity that allowed for measurements of effluxes across the apical or the basolateral membranes. 86Rb was used as an isotopic tracer to indicate potassium movements. The 86Rb+ efflux across the basolateral face was 1.93-times that across the apical face, and both effluxes were pH dependent. Apical and basolateral 86Rb+ effluxes increased when the Ca2+ ionophore ionomycin (3 microM) was applied and when monolayers were exposed to a hypotonic medium. A pharmacological study revealed that BaCl2 (5 mM), tetraethylammonium (TEA, 20 mM) and Leiurus quinquestriatus hebraeus scorpion venom (from which charybdotoxin is extracted) abolished both ionomycin and hypotonically-stimulated effluxes, whereas apamin had no significant effect on the hypotonically-stimulated 86Rb+ efflux. This stimulated efflux was also abolished when monolayers were preincubated with pertussis toxin, but did not decrease in a Ca2(+)-free medium.

Animals↗
PubMed1992

Transbilayer incorporation of 1-pyrenebutyltrimethylammonium by blood platelets and its application for analyzing changes in physico-chemical properties of the membrane lipid bilayer induced by platelet activation.

The binding of cationic butyltrimethylammonium derivative of pyrene to bovine platelets was initially rapid and then increased gradually, unlike the bindings of other anionic and neutral derivatives of pyrene tested. The rate of increase in binding of the cationic probe depended on temperature and was due to its incorporation into the cytoplasmic side of the platelet membranes, as shown quantitatively by monitoring decrease in its extractability with albumin. The penetration into the inner membrane compartment did not reach equilibrium even after 4 h at 37 degrees C. Slow penetration of a fluorescent probe such as this is useful in studies on the physico-chemical properties of the outer layer and cytoplasmic side of the platelet membranes and their changes. Initial rapid binding of the cationic probe to platelets, representing the binding of the probe to the outer layer of the plasma membrane, was increased by ionomycin-induced platelet activation. Fluorescence spectra in the presence of a relatively high concentration of the cationic probe showed increase of the excimer of the cationic probe accompanied with the incorporation of the probe to the cytoplasmic side. On ionomycin-induced activation, the excimer-to-monomer intensity ratio of the probe in the cytoplasmic side of the platelet membranes decreased, possibly due to decrease in fluidity of the lipid layer near the probe or change in distribution of the probe.

Animals↗
PubMed1995

Differential signal transduction pathways regulating interleukin-2 synthesis and interleukin-2 receptor expression in stimulated human lymphocytes.

In human peripheral blood lymphocytes stimulated via the T-cell antigen receptor/CD3 complex IL-2 synthesis and cellular proliferation were effectively inhibited by a concentration of ouabain as low as 50 nM, whilst the expression of high affinity IL-2 receptors was not influenced. Binding of the monoclonal antibody, BMA 031 to the T-cell antigen receptor/CD3 complex resulted in a bimodal activation of protein kinase C. The activation of protein kinase C-alpha in the early phase of T-lymphocyte activation was not affected by 50 nM ouabain, in contrast sustained activation of protein kinase C-beta, between 90-240 min of stimulation was completely abolished by the cardiac glycoside. When protein kinase C was directly activated by PMA + ionomycin, 50 nM ouabain was ineffective in inhibiting protein kinase C activation, as well as subsequent IL-2 synthesis, suggesting that the glycoside interfered with signal transducing mechanism(s) upstream of the activation of protein kinase C. Ouabain had no influence on the elevation of intracellular calcium concentration in BMA 031 stimulated lymphocytes, ruling out the possibility that it interfered with the T-cell antigen receptor dependent phosphatidylinositol response. In contrast, lysophosphatide acyltransferase catalysed elevated incorporation of polyunsaturated fatty acids was effectively inhibited by low concentrations of ouabain in BMA 031-stimulated T-lymphocytes, whereas stimulation with PMA + ionomycin had no influence on the plasma membrane phospholipid fatty acid metabolism. These results suggest, that differential signal transduction pathways are involved in the activation of protein kinases C-alpha and -beta. They implicate that elevated incorporation of polyunsaturated fatty acids into plasma membrane phospholipids might contribute to sustained activation of protein kinase C-beta, and establish a link between activation of protein kinase C-beta and induction of IL-2 synthesis in human lymphocytes.

Biological Transport↗
PubMed1986

Redistribution of protein kinase C during mitogenesis of human B lymphocytes.

G0 human tonsillar B-lymphocytes were stimulated to divide by the polyclonal mitogen Staphylococcus Aureus Cowan strain 1 (SAC) and by the combined use of 12-O-tetradecanoyl phorbol-13-acetate (TPA) and the calcium ionophore ionomycin. The activities of protein kinase C, which requires Ca++ and phospholipid as co-factors, and a proteolytically cleaved form of this enzyme (protein kinase M), which is independent of calcium and phospholipid control, were determined in soluble and particulate fractions obtained from activated B cells. Treatment of G0 B cells with SAC or TPA together with ionomycin caused redistribution of protein kinase C from the soluble to the particulate fraction where the 80,000-Dalton protein kinase C was cleaved to give rise to a 50,000-Dalton form of the kinase which was also found in the cytoplasm. These data suggest that redistribution and proteolytic cleavage of protein kinase C are key signal transduction events in B cell mitogenesis.

B-Lymphocytes↗
PubMed1987

Cyclosporin A inhibits PGE2 release from vascular smooth muscle cells.

The influence of the fungoid undecapeptide cyclosporin A (CyA) on PGE2 release from cultured rat aortic smooth muscle cells was investigated in this study. We found that CyA time and concentration dependently (ED50:500 ng/ml) inhibited PGE2 release from the cells. CyA attenuated both basal and PGE2 release evoked by angiotensin II (10(-10)-10(-6) M), arginine vasopressin (10(-10)-10(-6) M) and ionomycin (10(-9)-10(-6) M). CyA (1 microgram/ml) did not affect the conversion of exogenous arachidonic acid (1 microM) into PGE2. The inhibitory effect of CyA was neutralized by high concentrations of the calcium ionophore ionomycin (greater than 3 X 10(-6) M). Taken together our results indicate that CyA inhibits both basal and vasoconstrictor evoked PGE2 release from vascular smooth muscle by impairing the availability of free arachidonic acid rather than by inhibiting the conversion of arachidonic acid into PGE2.

Angiotensin II↗
PubMed1988

Inhibition by iodide of iodide binding to proteins: the "Wolff-Chaikoff" effect is caused by inhibition of H2O2 generation.

H2O2 generation is limiting the oxidation and binding to proteins of iodide. In dog thyroid slices thyrotropin and carbamylcholine greatly enhance protein iodination and H2O2 generation. The action of thyrotropin is mimicked by dibutyryl cyclic AMP and forskolin which suggests that it is mediated by cyclic AMP. The action of carbamylcholine was mimicked by ionomycin and by phorbol myristate ester. This suggests that the effect of carbamylcholine is mediated by the two intracellular signals generated by the Ca++ phosphatidylinositol cascade: Ca++ and diacylglycerol. The Wolff-Chaikoff effect is the inhibition by iodide of its own organification. In dog thyroid slices, iodide greatly inhibited H2O2 generation stimulated by thyrotropin and by carbamylcholine. Iodide decreased the production of intracellular signals induced by TSH and carbamylcholine but it also inhibited the action of probes of these intracellular signals (dibutyryl cAMP, forskolin, ionomycin, phorbol-myristate ester) on the H2O2 generating system itself. These effects were suppressed by methimazole an inhibitor of iodide oxidation.

Animals↗
PubMed1992

High external Ca2+ levels trigger membrane potential oscillations in mouse pancreatic beta-cells during blockade of K(ATP) channels.

Glucose depolarizes the pancreatic beta-cell and induces membrane potential oscillations, but the nature of the underlying oscillatory conductance remains unknown. We have now investigated the effects of the Ca2+ ionophore ionomycin and high external Ca2+ concentration ([Ca2+]o) on glucose-induced electrical activity and whole islet intracellular free Ca2+ concentration ([Ca2+]i), under conditions where the K(ATP) channel was blocked (100 microM tolbutamide or 4 microM glibenclamide). Raising [Ca2+]o to 10.2 or 12.8 mM, but not to 5.1 or 7.7 mM, turned continuous electrical activity into bursting activity. High [Ca2+]o (12.8 mM) regenerated a pattern of fast [Ca2+]i oscillations overshooting the levels recorded in tolbutamide. Ionomycin (10 microM) raised the [Ca2+]i and synergized with 5.1 mM Ca2+ to hyperpolarize the beta-cell membrane. The data indicate that a [Ca2+]i-sensitive and sulphonylurea-insensitive oscillatory conductance underlies the beta-cell bursting activity.

Adenosine Triphosphate↗
PubMed1991

FK-506 and cyclosporin A: selective inhibition of calcium ionophore-induced polymorphonuclear leukocyte degranulation.

This paper investigates the abilities of FK-506 and cyclosporin A (CsA) to inhibit human polymorphonuclear leukocyte (PMNL) degranulation. PMNLs, purified from human blood, were stimulated in vitro with A23187, ionomycin, the complement derived peptide C5a, formylmethionylleucinylphenylalanine (FMLP) or phorbol myristate acetate (PMA). Degranulation was assessed by measuring the release of either lactoferrin or N-acetyl-beta-D-glucosaminidase (NAG). Both FK-506 and CsA produced a concentration-related inhibition of degranulation induced by either A23187 or ionomycin but did not affect C5a-, FMLP- or PMA-induced degranulation. The IC50 values for inhibition of degranulation (approximately 0.7 nM for FK-506 and 33.7 nM for CsA) are very close to the published values for inhibition of human T-cell proliferation. Removal of calcium from the incubation medium with ethyleneglycolbis(aminoethylether)tetra-acetate (EGTA) totally inhibited calcium ionophore-induced degranulation but had no effect against C5a-, FMLP- or PMA-induced degranulation. Preincubation of PMNLs with actinomycin D or cycloheximide did not affect either A23187- or PMA-induced degranulation. Non-immunosuppressive analogs of CsA were ineffective at inhibiting degranulation. Rapamycin, a macrolide structurally related to FK-506, did not inhibit degranulation but it did antagonize the inhibition produced by FK-506. Given the similar profiles of activity of FK-506 and CsA in neutrophils and T cells, we conclude that similar activation or signal transduction pathways may be present in both T cells and neutrophils. Because A23187-induced PMNL degranulation was not sensitive to either actinomycin D or cycloheximide, it is apparent that the signal transduction pathways ultimately control different cellular functions.

Anti-Bacterial Agents↗
PubMed1994

Effects of membrane depolarization and changes in intra- and extracellular calcium concentration on phosphoinositide hydrolysis in bovine tracheal smooth muscle.

Agonist-stimulated phosphoinositide metabolism plays a central role in pharmacomechanical coupling in airways smooth muscle (ASM). In many other tissues and cells, most noteably excitable cells, membrane depolarization or an increase in intracellular Ca2+ ([Ca2+]i) generated by inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-induced Ca2+ release or agonist-mediated Ca2+ influx is able to trigger or augment phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) hydrolysis and/or initiate PtdIns4P/PtdIns hydrolysis by direct stimulation of PIC. To assess the importance of these mechanisms in ASM the effects of KCl-induced membrane depolarization, extracellular Ca2+ ([Ca2+]e) chelation, and addition of ionomycin to elevate [Ca2+]i on basal and agonist-stimulated Ins(1,4,5)P3 concentration and [3H]-InsPx accumulation have been examined. Reducing [Ca2+]e from 1.8 mM to 6 or 0.8 microM caused a progressive inhibition of agonist-stimulated [3H]inositol polyphosphate accumulation over 30 min with the histamine-stimulated response being significantly more sensitive to [Ca2+]e chelation than the response to carbachol. In contrast, the initial accumulation of Ins(1,4,5)P3 was completely unaffected by such reductions in [Ca2+]e. Incubation of [3H]inositol-prelabelled BTSM slices with buffer containing 80 mM KCl failed to stimulate [3H]InsPx accumulation, causing instead a small inhibition of carbachol-stimulated [3H]InsPx accumulation with a similar effect seen with respect to Ins(1,4,5)P3 accumulation. Addition of 5 microM ionomycin to BTSM slices similarly did not stimulate Ins(1,4,5)P3 generation and only increased [3H]InsPx accumulation after prolonged stimulation in the presence of high (mM) [Ca2+]e. These data indicated that in ASM, membrane depolarization or physiological increases in [Ca2+]i did not result in either independent activation of PIC or augmentation of initial agonist-stimulated PtdIns(4,5)P2 hydrolysis. However, while the initial agonist-stimulated generation of Ins(1,4,5)P3 was not dependent on [Ca2+]e, a normal plasmalemmal Ca2+ gradient was required to sustain maximal rates of agonist-stimulated PtdIns(4,5)P2 hydrolysis.

Animals↗