Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Whole-cell recordings were made from submucosal neurones acutely dissociated from guinea-pigs. The actions of noradrenaline, somatostatin and [Met5]enkephalin on currents carried by calcium ions were studied. 2. On depolarization from a holding potential of -70 mV, an inward current activated at -40 mV, reached its peak amplitude at 10 mV and reversed to outward at 72 mV (with external calcium of 5 mM and internal caesium of 160 mM). 3. Cadmium, nickel and cobalt reversibly blocked the calcium current; concentrations causing 50% block were 2.5, 500 and 2000 microM respectively. The calcium current (holding at -70 or -30 mV) was reversibly blocked by omega-conotoxin (100 nM), and unaffected by Bay K 8644 (0.1-10 microM) and nifedipine (1 microM). Cadmium caused an outward shift in holding current at -30 mV, implying that there was a persistent inward calcium current at this potential. 4. Noradrenaline, somatostatin and [Met5]enkephalin decreased the calcium current. The maximal inhibition observed with any one agonist, or with a combination of two agonists, did not exceed 50%; concentrations giving half-maximal inhibition were 5.5 microM for noradrenaline, 4 nM for somatostatin and 1 microM for [Met5]enkephalin. The inhibition was independent of membrane potential. All three agonists also reduced the persistent calcium current at -30 mV. 5. Inhibition of the calcium current by noradrenaline occurred with a latency of not less than 175 ms; cadmium applied by the same method depressed the current within 5-45 ms. 6. Experiments with selective agonists and antagonists indicated that the receptor types involved in calcium current inhibition were alpha 2-adrenoceptors and delta-opioid receptors. Somatostatin acted at a distinct receptor. 7. Calcium currents were also inhibited by intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S). Agonists were ineffective in cells pre-treated with pertussis toxin, but their action was restored when purified GTP-binding proteins (Go or Gi) were included in the intracellular recording solution. 8. It is concluded that noradrenaline, somatostatin and [Met5]enkephalin act at their respective receptors on guinea-pig submucosal neurones to inhibit a voltage-dependent calcium current. Activation of the same receptors also increases a potassium conductance in these cells: in both cases a pertussis-sensitive G protein is involved.
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PMID:Inhibition of calcium currents by noradrenaline, somatostatin and opioids in guinea-pig submucosal neurones. 198 21

In bovine adrenal glomerulosa cells, angiotensin-II (AII) induced a biphasic increase in 1,2-sn-diacylglycerol (DAG), with an initial peak at 10 sec followed by a transient decrease at 30 sec. The second increase was much higher in magnitude than the first peak and reached its maximum after 1 h of stimulation. Such kinetics of DAG formation resemble those with which AII stimulates the formation of inositol-1,4,5-trisphosphate. The protein synthesis inhibitor cycloheximide, which prevents hormone-induced de novo phospholipid synthesis in adrenal fasciculata cells, had no effect on the DAG response to Aii. The first phase of signal generation of both inositol-1,4,5-trisphosphate and DAG was not affected by incubation in calcium-deficient extracellular medium. However, the second phase of the inositol phosphate response was almost completely inhibited in low calcium medium, while the DAG response was reduced by only one third. Pertussis toxin (150 ng/ml) and the voltage-sensitive calcium channel inhibitors, nifedipine (1 microM) and Ni2+ (100 microM), had no effect on the DAG response to AII. The retention of a substantial DAG response to AII in low calcium medium, with concomitant diminution of the inositol phosphate response, indicates that a major part of the DAG formed during the sustained phase of hormonal stimulation is derived from sources other than phosphoinositides. The DAGs produced from different phospholipids could have distinctive fatty acid compositions and membrane localizations, which, in turn, could result in the differential activation of protein kinase-C. In this way, the increased complexity of the hormonally induced signalling pathway could allow for a greater diversity of responses in hormone-stimulated target cells.
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PMID:Regulation of 1,2-diacylglycerol production by angiotensin-II in bovine adrenal glomerulosa cells. 215 15

The effects of dopamine (DA) on voltage-dependent Ca2+ currents were investigated in cultured rat lactotroph cells using the patch clamp recording technique. Each recorded cell was identified by the reverse hemolytic plaque assay. In the whole-cell configuration, two types of Ca2+ currents, L and T, were characterized on the basis of their kinetics, voltage sensitivity, and pharmacology. The L component had a threshold of -25 mV, showed little inactivation during a 150-msec voltage step, and was maximal at +10 mV. Cadmium ions (100 microM) significantly reduced its amplitude (75%). The T component was activated at a membrane potential close to -50 mV, was maximal at -10 mV, and showed a voltage-dependent inactivation between -90 and -30 mV. It was quickly inactivated during a maintained depolarization (time constant, 27 ms at -30 mV) and was strongly reduced (80%) by nickel ions (100 microM). Bath application of DA (10 nM) caused a markedly general depression of inward Ca2+ currents, acting differently on the T- and L-type currents. DA application shifted the voltage-dependence of the L-type current activation toward depolarization values (8 mV) without modifying its time- and voltage-dependent inactivation. In contrast, DA enhanced the inactivation of the T-type current by accelerating its time-dependent inactivation (25% decrease in the time constant of inactivation) and by shifting the voltage-dependence of the T-type current inactivation toward hyperpolarizing values (-63 mV in control vs. -77 mV in the presence of DA). These effects of DA were dose-dependent and involved the activation of a D2 receptor type. They were mimicked by bromocriptine application (10 nM), whereas sulpiride (100 nM) blocked the DA-evoked response. The D1 antagonist SCH 23390 was ineffective up to 100 microM. All of these DA-induced modifications in Ca2+ currents were abolished using a GTP-free pipette solution or after pretreatment of cells with pertussis toxin, suggesting that DA can regulate the function of Ca2+ channels through GTP-binding proteins (G-proteins). Our results show that DA acts simultaneously by reducing both voltage-dependent Ca2+ currents on lactotroph cells. Thus, DA reduces the entry of Ca2+ ions across the surface membrane and thereby influences electrical activity and the cytosolic free Ca2+ concentration involved in both basal and evoked PRL release.
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PMID:Dopamine inhibits two characterized voltage-dependent calcium currents in identified rat lactotroph cells. 216 20

Agonist-stimulated divalent cation entry was studied in fura-2-loaded hepatocytes. In the presence of extracellular Mn2+, the Ca2(+)-mobilizing hormone vasopressin produced a severalfold stimulation of the basal rate of fura-2 fluorescence quenching as a result of Mn2+ influx; this effect was blocked by the presence of Ni2+ in the incubation medium. Half-maximum and maximum stimulation of Mn2+ influx was observed with 0.1 and 0.8 nM vasopressin, respectively. Agonist-stimulated Mn2+ influx was also seen with angiotensin II, ATP, phenylephrine, and the combination of AlCl3 and NaF. The stimulation of Mn2+ influx did not occur immediately after addition of Ca2(+)-mobilizing agents, but was characterized by a latency period of 20-30 s. In contrast to vasopressin, glucagon did not stimulate Mn2+ influx into hepatocytes, but produced both a 3-fold enhancement of the rate of vasopressin-stimulated Mn2+ entry and the abolishment of the latency period. The effects of glucagon were mimicked by forskolin and dibutyryl cAMP. Pretreatment of hepatocytes with pertussis toxin or depolarization of the cells altered neither the basal rate of Mn2+ entry nor the ability of vasopressin to stimulate this rate. Emptying of the inositol 1,4,5-trisphosphate-sensitive Ca2+ store by treatment with 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) did not enhance Mn2+ entry into hepatocytes; however, exposure of the cells to tBuBHQ for 2 min markedly enhanced the ability of vasopressin, alone or in combination with glucagon, to increase the rate of Mn2+ influx. Furthermore, pretreatment with tBuBHQ for 2 min abolished the latency of vasopressin-stimulated Mn2+ influx. It is concluded that Ca2(+)-mobilizing hormones stimulate Ca2+ influx in hepatocytes, possibly through receptor-operated Ca2+ channels. The stimulation of divalent cation entry is transduced by a G protein, and the rate of influx appears to be controlled both by the intracellular level of cAMP and the empty state of an intracellular Ca2+ pool that may be inositol 1,4,5-trisphosphate-insensitive.
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PMID:Receptor-operated calcium influx in rat hepatocytes. Identification and characterization using manganese. 217 Mar 82

The mechanisms of action of two different serotonin receptors, found in a neuronal cell line (neuroblastoma X glioma hybrid cells) and in a non-excitable glioma cell line, were explored. In both cell lines, serotonin induced a dose-dependent, transient rise of cytosolic Ca2+ activity (measured by fura-2 or indo-1 fluorescence). Ca2+ channel blockers (Ni2+ and La3+, not nifedipine) suppressed the Ca2+ response to serotonin in the hybrid cells but not in the glioma cells. After application of Ca2+ ionophores (ionomycin and A23187) in order to short-circuit internal Ca2+ stores, serotonin was still able to induce a Ca2+ response in the hybrid cells but not in the glioma cells. Serotonin dose-dependently stimulated the rate of 45Ca2+ uptake several-fold in the hybrid cells, but hardly at all in the glioma cells. Thus, in the neuronal cell line cytosolic Ca2+ activity is raised through enhancement of Ca2+ entry into the cells from the extracellular environment via 5-HT3 receptors (blocked by ICS 205-930, MDL 72222 and GR 38032 F). The depolarization response caused by serotonin in the hybrid cells is due to activation of cation conductance(s), obviously allowing entry of extracellular Ca2+. In contrast to the neuronal cell line, in the glial cell line the rise of Ca2+ activity is mediated by ketanserin-susceptible 5-HT2 receptors (not affected by treatment with pertussis toxin) mainly liberating Ca2+ from internal stores. In the glioma cells the release of Ca2+ from internal stores leads to opening of Ca2+-dependent K+ channels, responsible for the hyperpolarizing response. Thus, the neuronal and the glial cell lines might provide suitable systems in which to study the diverse cellular functions triggered by the rise of cytosolic Ca2+ activity, which is caused by different serotonin receptors.
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PMID:Serotonin regulates cytosolic Ca2+ activity and membrane potential in a neuronal and in a glial cell line via 5-HT3 and 5-HT2 receptors by different mechanisms. 260 42

The increase in intracellular free Ca2+ ([Ca2+]i) associated with interaction of monocyte chemotactic protein-1 (MCP-1) and related chemokines beta with adherent human blood monocytes was investigated at the single-cell level. We used f-MLP as reference chemotactic agent. MCP-1 caused an increase in [Ca2+]i in individual adherent monocytes, with 95% of cells responding to the chemokine at 20 ng/mL. Response to MCP-1 was already detectable at 1 pg/mL, whereas at least 5 ng/mL were required for significant chemotactic response. The kinetics of the increase in [Ca2+]i were considerably different for MCP-1 compared with f-MLP. MCP-1 produced a slow increase of [Ca2+]i that reached a plateau in 5 to 7 minutes. On the other hand, the increase of [Ca2+]i induced by f-MLP appeared to be biphasic, with a fast phase peaking after 5 to 40 seconds followed by a slower wave. Blocking of Ca2+ channels by Ni2+ or Cd2+ and/or chelation of extracellular free Ca2+ considerably reduced but did not abolish response to MCP-1, had no effect on the first wave of [Ca2+]i induced by f-MLP, and completely abrogated the second, slower wave. Thapsigargin, which empties intracellular Ca2+ stores, inhibited f-MLP-induced [Ca2+]i increase but fully blocked the action of MCP-1 only when combined with Ni2+. Thus, increase of [Ca2+]i induced by MCP-1 is apparently due to independent opening of a channel and mobilization from intracellular stores, whereas f-MLP-induced mobilization of Ca2+ from stores causes subsequent opening of a channel. At variance with MCP-1, the related chemokine MCP-2 induced only a low increase of [Ca2+]i in about 40% of adherent monocytes. Inhibition of chemokine-induced increase of [Ca2+]i by cholera or pertussis toxin indicated that MCP-1 and MCP-2 activate monocytes through different intracellular pathways. These results demonstrate at the single-cell level that the mechanisms and dynamics of increased [Ca2+]i are considerably different for f-MLP and chemokines beta. In addition, the [Ca2+]i increase induced by the two related chemokines beta MCP-1 and MCP-2 appears to be differently regulated, suggesting interaction with distinct receptors.
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PMID:Single-cell analysis of macrophage chemotactic protein-1-regulated cytosolic Ca2+ increase in human adherent monocytes. 766 86

1. Regulation of membrane potential by extracellular Ca2+ concentration ([Ca2+]o) was examined in freshly isolated rabbit osteoclasts. 2. The resting membrane potential of osteoclasts was close to the K+ equilibrium potential in 1 mM Ca2+ medium. An elevation of [Ca2+]o caused membrane depolarization, accompanied by a decrease in the membrane conductance. 3. The inwardly rectifying K+ current observed under voltage clamp was dose-dependently inhibited by an elevation of [Ca2+]o, which explained the membrane depolarization caused by high [Ca2+]o. 4. Other divalent cations also inhibited the inwardly rectifying K+ current with the following order of potency: Ca2+ < Ni2+ < or = Co2+ < Cd2+. 5. In the presence of intracellular GTP gamma S the inwardly rectifying K+ current was irreversibly inhibited by [Ca2+]o, whereas the inhibition of the inwardly rectifying K+ current was greatly attenuated by intracellular application of GDP beta S. 6. Pertussis toxin (PTX) treatment did not abolish the inhibition of the inwardly rectifying K+ current caused by [Ca2+]o. 7. These results suggest that inwardly rectifying K+ channels in osteoclasts were regulated by a PTX-insensitive G-protein, which was coupled to the putative Ca2+ receptor or sensor on the cell membrane.
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PMID:Inhibition of inwardly rectifying K+ current by external Ca2+ ions in freshly isolated rabbit osteoclasts. 786 41

Sarafotoxin b (S6b)-induced changes in intracellular Ca2+ concentration ([Ca2+]i) were monitored in cultured canine tracheal smooth muscle cells (TSMCs) by a fluorescent Ca2+ indicator fura-2. S6b elicited an initial transient peak followed by a sustained elevation of [Ca2+]i. BQ-123, an endothelin-A (ETA) receptor antagonist, had a high affinity to block the rise in [Ca2+]i response to S6b. In the absence of external Ca2+, only an initial transient peak of [Ca2+]i was seen, the sustained elevation of [Ca2+]i could then be evoked by addition of 1.8 mM Ca2+. Ca2+ influx was required for the changes of [Ca2+]i, since the Ca(2+)-channel blockers, diltiazem, verapamil, and Ni2+, decreased both the initial and sustained elevation of [Ca2+]i in response to S6b. TSMCs pretreated with phorbol 12-myristate 13-acetate (PMA, 1 microM) for 30 min attenuated Ca2+ mobilization induced by S6b, which was reversed by staurosporine, a protein kinase C (PKC) inhibitor. The change of [Ca2+]i induced by S6b was attenuated by cholera toxin pretreatment, but not by pertussis toxin. These data demonstrate that the initial detectable increase in [Ca2+]i stimulated by S6b is due to the activation of ETA receptors and subsequent release of Ca2+ from internal stores, whereas the contribution of external Ca2+ follows and partially involves a diltiazem- and verapamil-sensitive process. The inhibition of PMA on S6b-induced Ca2+ mobilization was inversely correlated with membraneous PKC activity.
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PMID:Sarafotoxin-induced calcium mobilization in cultured dog tracheal smooth muscle cells. 787 38

N-Formyl-methionyl-leucyl-phenylalanine (fMLP) is able to accelerate Ca2+ entry into differentiated HL60 cells by a rather indirect mechanism consisting of the opening of a plasma membrane pathway activated by the emptying of the intracellular Ca2+ stores caused by the agonist. This Ca2+ pathway can also be fully activated by Ca2+ store depletion with thapsigargin. We show here that, in addition to this store-operated Ca2+ entry pathway (SOCP), fMLP is able to activate another receptor-operated Ca2+ pathway in thapsigargin-treated HL60 cells differentiated for 24 h with dimethyl sulfoxide. Activation by fMLP was produced even in cells with fully empty Ca2+ stores. It started 30 s after fMLP addition, was maximal after 2 min and then disappeared within 5 min. This pathway was similar to SOCP in that it allowed passage of Mn2+ and Ba2+ and was antagonized by Ni2+ and by cytochrome P-450 inhibitors. fMLP is also able to inhibit SOCP by a mechanism involving protein phosphorylation. Both the fMLP-induced activation of Ca2+ entry and the inhibition of SOCP were prevented by pretreatment with pertussis toxin. However, the first appeared earlier than the last along differentiation of HL60 cells. This suggests that the inhibition of SOCP requires not only the development of fMLP receptors but also an additional component placed distally to the G protein in the transduction mechanism.
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PMID:Activation by chemotactic peptide of a receptor-operated Ca2+ entry pathway in differentiated HL60 cells. 796 26

The signaling mechanisms underlying neurite growth induced by cadherins and integrins are incompletely understood. In our experiments, we have examined these mechanisms using purified N-cadherin and laminin (LN). We find that unlike the neurite growth induced by fibroblastic cells expressing transfected N-cadherin (Doherty, P., and F.S. Walsh. 1992. Curr. Opin. Neurobiol. 2:595-601), growth induced by purified N-cadherin in chick ciliary ganglion (CG), sensory, or forebrain neurons is not sensitive to inhibition by pertussis toxin. Using fura-2 imaging of single cells, we show that soluble N-cadherin induces Ca2+ increases in CG neuron cell bodies, and, importantly, in growth cones. In contrast, N-cadherin can induce Ca2+ decreases in glial cells. N-cadherin-induced neuronal Ca2+ responses are sensitive to Ni2+, but are relatively insensitive to diltiazem and omega-conotoxin. Similarly, neurite growth induced by purified N-cadherin is inhibited by Ni2+, but is unaffected by diltiazem and conotoxin. Soluble LN also induced small Ca2+ responses in CG neurons. LN-induced neurite growth, like that induced by N-cadherin, is insensitive to diltiazem and conotoxin, but is highly sensitive to Ni2+ inhibition. K+ depolarization experiments suggest that voltage-dependent Ca2+ influx pathways in CG neurons (cell bodies and growth cones) are largely blocked by the combination of diltiazem and Ni2+. Our results demonstrate that cadherin signaling involves cell type-specific Ca2+ changes in responding cells, and in particular, that N-cadherin can cause Ca2+ increases in neuronal growth cones. Our findings are consistent with the current idea that distinct neuronal transduction pathways exist for cell adhesion molecules compared with integrins, but suggest that the involvement of Ca2+ signals in both of these pathways is more complex than previously appreciated.
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PMID:Ca2+ influx and neurite growth in response to purified N-cadherin and laminin. 796 2


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