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At least 883 records · Page 49Linked to original sources
PubMed1993

Inositol phosphate formation and release of intracellular free calcium by bradykinin in HaCaT keratinocytes.

Phospholipase C-mediated release of inositol trisphosphate, followed by an increase in free intracellular calcium, is an important signal transduction pathway for several membrane receptors. In the present investigation, the coupling of various receptors to phospholipase C was studied in the human keratinocyte line HaCaT. Inositol trisphosphate formation was determined by anion-exchange chromatography, and the release of intracellular calcium was analysed with the fluorescence probe Fura-2 AM. Activation of HaCaT keratinocytes with bradykinin resulted in a time- and dose-dependent release of inositol trisphosphate and intracellular calcium, with an EC50 value of 50 nM for bradykinin-induced inositol trisphosphate formation. The mediators and cytokines IL-1, IL-4, IL-6, IL-8, EGF and TGF alpha, as well as bombesin, prolactin, carbachol, substance P and retinoic acid, did not activate this pathway. The inability of the mediators examined to activate phospholipase C may be due to lack of the respective cognate receptors or to the use of other signal transduction pathways.

Bradykinin↗
PubMed1994

The glutamate inhibition of carbachol stimulated inositol phosphate production in rat cortical cells is mediated through an ionotropic NMDA receptor.

Carbachol (0.1 mM) stimulated accumulation of inositol monophosphate (IP1) (3-4 fold of basal, P < 0.001) in fetal rat cortical cells is attenuated by glutamate (at 0.1 mM, 40-70% of carbachol alone, P < 0.001). This inhibition by glutamate was reduced by 2-amino-5-phosphonopentanoic acid (AP5), but not by gamma-D-glutamylaminomethyl sulphonic acid (GAMS) [corrected] or 2-amino-3-phosphonopropionic acid (AP3). The metabotropic receptor agonist (1S,3R)-1-aminocyclopentane-1-3-dicarboxylic acid [(1S,3R)-ACPD] (up to 0.1 mM) had no effect upon carbachol stimulated IP1. Staurosporine and quinacrine were unable to prevent the inhibition of carbachol stimulated IP1 by glutamate. These data suggest that the inhibition of carbachol-stimulated IP1, by glutamate in rat cortical cells is mediated through an NMDA ionotropic receptor.

Animals↗
PubMed1988

Intracellular calcium translocation: mechanism of activation by guanine nucleotides and inositol phosphates.

The movements of Ca2+ within cells in response to external stimuli are complex. Internal Ca2+ release activated by inositol 1,4,5-trisphosphate (InsP3) is now widely established. However, the mechanism of InsP3-induced Ca2+ release, the identity and control of the InsP3-sensitive Ca2+ pool and its relationship to other internal and external Ca2+ pools all remain uncertain. We have characterized a highly sensitive and specific guanine nucleotide-regulatory mechanism that induces rapid and profound movements of intracellular Ca2+ via a mechanism distinct from that activated by InsP3. Using permeabilized neural or smooth muscle cells, application of submicromolar concentrations of GTP induces rapid release of Ca2+ from a compartment that contains within it the InsP3-releasable Ca2+ pool. Although of similar GTP-sensitivity as G-protein-activated events, the apparent dependence on GTP hydrolysis and blockade by GTP gamma S suggest a mechanism distinct from those mediated by known G-proteins. Recent experiments in the presence of oxalate reveal rapid and profound GTP-activated uptake of Ca2+ via a mechanism with identical nucleotide sensitivity and specificity to GTP-induced Ca2+ release. These results were interpreted to suggest that GTP induces a transmembrane conveyance of Ca2+ between different compartments distinguished by oxalate permeability; GTP-induced release probably occurs via a similar mechanism except involving transfer between closed compartments and nonclosed membranes (perhaps the plasma membrane). Recently, it has been revealed that GTP activates a translocation of Ca2+ into the Ca2+ pool from which InsP3 induces release. This is an important observation suggesting that the GTP-activated Ca2+ translocation process may control entry into and hence the size of the InsP3-releasable Ca2+ pool. Indeed, it is possible that GTP-induced Ca2+ release observed in permeabilized cells reflects a reversal of the pathway that functions in intact cells to permit external Ca2+ entry into the InsP3-releasable pool. This type of process could mediate the longer-term secretory or excitatory responses to external receptors which are known to be dependent on external Ca2+.

Animals↗
PubMed1988

Effects of inositol phosphates on the membrane activity of smooth muscle cells of the rabbit portal vein.

The effects of intracellular perfusion of inositol 1,4,5-trisphosphate (InsP3) or inositol 1,3,4,5-tetrakisphosphate (InsP4) on electrical responses of smooth muscle cell membranes of the rabbit portal vein were studied using the whole cell voltage clamp technique. Depolarisation to 0 mV from a holding potential of -60 mV, evoked inward Ca (Ica), transient outward (ISO), oscillatory outward (IOO) and sustained outward (ISO) currents. Generation of IOO was dependent on the [Ca]o, but it was also generated in 0 mM Ca solution for over 10 min. From amplitude histograms, IOO was divided into two components. Reduction in [Ca]o inhibited the appearance of but not the amplitudes of both IOO components. However, the larger component of IOO was more resistant to a reduction in [Ca]o than the smaller one. InsP3 (10 microM) increased the frequency of both IOO components to a greater extent than their amplitude, but the larger component was more sensitive to InsP3 than the smaller one. The increase in the occurrence of IOO induced by InsP3 did not occur following pretreatment with 3 mM caffeine or 1 nM A23187. In normal PSS, InsP3 was evoked by a depolarising pulse positive to -40 mV, whereas following perfusion with InsP3 (10 microM), IOO was evoked at -60 mV. In normal PSS, intracellular perfusion with 10 microM InsP4 changed neither the frequency nor the amplitude of IOO, and the amplitudes of ICa, ITO and ISO were also unchanged. However, in 10 mM Ca solution, 10 microM InsP4 generated IOO at a membrane potential of -60 mV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Stimulation by epidermal growth factor of inositol phosphate production in plasma membranes from A431 cells.

Plasma membranes were isolated from A431 cells previously labelled with myo-[3H]inositol during exponential growth, using a rapid procedure on Percoll gradients. They displayed a significant phospholipase (PLC) activity against phosphoinositides, which was stimulated by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), epidermal growth factor (EGF) and fetal calf serum (FCS) (24%, 11% and 97% over controls, respectively). The effect of EGF was not significantly increased by GTP gamma S. Upon addition of cytosol, EGF promoted an almost 100% stimulation of inositol 1,4,5-trisphosphate and inositol bisphosphate generation, which displayed an absolute requirement for GTP gamma S. This dose-dependent effect of cytosol was linear until 60 micrograms/ml of cytosolic protein and decreased afterwards; it was abolished by heat treatment and trypsin hydrolysis, and it was not reproduced by an identical amount of bovine serum albumin. The same biphasic stimulation was observed with phosphotyrosyl proteins immunopurified from cytosol of A431 cells previously stimulated by EGF. Since phosphotyrosyl proteins displayed PLC activity, our data suggest that soluble protein substrates of EGF receptor tyrosine kinase, including PLC, could be involved in the regulation of phosphoinositide hydrolysis in response to EGF. Using phosphatidyl[3H]inositol 4,5-bisphosphate (PIP2) dispersed with unlabelled phosphatidylethanolamine and phosphatidylserine as an exogenous substrate, no stimulation of PLC activity by EGF could be detected, either with membranes or with membranes plus cytosol. It is concluded that EGF might stimulate hydrolysis of phosphoinositides by PLC through complex interactions between plasma membrane and cytosolic factors which still remain to be identified.

Cell Membrane↗
PubMed1989

Characterization of agonist-stimulated incorporation of myo-[3H]inositol into inositol phospholipids and [3H]inositol phosphate formation in tracheal smooth muscle.

The effects of the muscarinic agonist carbachol, histamine and bradykinin on incorporation of [3H]inositol into the phosphoinositides and the formation of [3H]InsPs were examined in bovine tracheal smooth-muscle (BTSM) slices labelled with [3H]inositol. These agonists result in substantial and dose-related increases in the incorporation of [3H]inositol into the phospholipids. Carbachol and histamine stimulated the incorporation of [3H]inositol into the phospholipids to the same degree, despite histamine being only 35% as effective as carbachol on [3H]InsP accumulation. Histamine and carbachol, at maximal concentrations, were non-additive with respect to both the stimulated incorporation of [3H]inositol and [3H]InsP formation. For carbachol this effect on incorporation was found to occur to a similar extent in PtdInsP and PtdInsP2 as well as PtdIns. The initial effect of carbachol on [3H]inositol incorporation was rapid (maximal by 10 min); however, with prolonged stimulation large secondary declines in PtdInsP and PtdInsP2 labelling were observed, with depletion of the much larger PtdIns pool only evident in the presence of Li+. Lowering buffer [Ca2+] increased the incorporation of [3H]inositol under basal conditions, but did not attenuate the subsequent agonist-stimulated incorporation effect. The large changes in specific radioactivity of the phosphoinositides, and consequently the [3H]InsP products, after carbachol stimulation resulted in the apparent failure of atropine to reverse the [3H]InsP response completely. Labelling muscle slices with [3H]inositol in the presence of carbachol or labelling for longer periods (greater than 6 h) prevented subsequent carbachol-stimulated effects on incorporation without significantly altering the dose-response relationship for carbachol-stimulated [3H]InsP formation and resulted in steady-state labelling conditions confirmed by the ability of atropine to reverse fully the [3H]InsP response to carbachol. This study demonstrates the profound effects of a number of agonists on [3H]inositol incorporation into the phospho- and polyphosphoinositides in BTSM with important consequent changes in the specific radioactivity of these lipids and the resulting [3H]InsP products. In addition, a selective depletion of PtdInsP and PtdInsP2 over PtdIns has been demonstrated with prolonged muscarinic-receptor stimulation.

Animals↗