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)

The ability of cations to modulate the binding of the sigma 1 receptor-selective ligand (+)-[3H]pentazocine to guinea pig cerebellum was investigated. Di- and trivalent cations biphasically inhibited (+)-[3H]pentazocine binding, revealing multiple affinity states. The rank order of potency of these cations (based on the high affinity component of inhibition) was Zn2+ > Co2+ >> La3+ = Ni2+ = Cd2+ = Mn2+ = Gd2+ > Ba2+ = Sr2+ >> Mg2+ > Ca2+. The inhibition of 1,3-[3H]di(2-tolyl)guanidine binding to the sigma 2 receptor by these cations differed qualitatively and quantitatively from their effects on (+)-[3H]pentazocine binding. Although monovalent cations decreased the Kd for (+)-[3H]pentazocine binding, divalent cations split (+)-[3H]pentazocine binding into low and high affinity components. The Bmax of the high affinity component decreased with increasing divalent cation concentrations. Both mono- and divalent cations significantly reduced the rate of association of (+)-[3H]pentazocine with the sigma 1 receptor without altering the dissociation rate. (+)-[3H]Pentazocine binding was not altered by guanine nucleotides or by treatment with cholera or pertussis toxins. However, nonselective cation channel blockers (cinnarizine, hydroxyzine, prenylamine, amiodarone, and proadifen) potently inhibited (+)-[3H]pentazocine binding. These results indicate that physiologically relevant concentrations of divalent cations allosterically modulate (+)-[3H]pentazocine binding to the sigma 1 receptor, to reveal multiple affinity states. These sites do not represent sigma 1 to sigma 2 subtype interconversion or ternary complex formation with guanine nucleotide-binding proteins. However, the rank order of cation potency and the inhibition of binding by cation channel blockers is consistent with a potential role for sigma receptors as constituents of cation channels.
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PMID:Modulation of (+)-[3H]pentazocine binding to guinea pig cerebellum by divalent cations. 127 78

The pluripotent human erythroleukaemia cell line, HEL, possesses erythrocytic, megakaryocytic and macrophage-like properties. With respect to signal transduction, HEL cells have been used as a model system for platelets, but little attention has been paid to their phagocytic properties. We studied the effects of various receptor agonists on the intracellular free Ca2+ concentration ([Ca2+]i) in HEL cells. Thrombin, platelet-activating factor (PAF), ATP, UTP, prostaglandins E1 and E2 (PGE1 and PGE2), the PGE2 analogue sulprostone and the stable PGI2 analogues iloprost and cicaprost increased [Ca2+]i. ADP was less effective than ATP, and UDP was unable to increase [Ca2+]i. The increases in [Ca2+]i induced by thrombin, PAF, ATP, UTP, iloprost and cicaprost were pertussis toxin-insensitive, whereas the increases induced by PGE2 and sulprostone were completely inhibited by the toxin. The increase in [Ca2+]i induced by PGE1 was partially inhibited by pertussis toxin. PGE2 did not desensitize the increase in [Ca2+]i induced by iloprost, and vice versa. PGE1 desensitized the response to PGE2 and iloprost but not vice versa. Adrenaline potentiated the iloprost- but not the PGE2-induced rise in [Ca2+]i. The phorbol ester phorbol 12-myristate 13-acetate completely blocked the rise in [Ca2+]i induced by ATP and PGE1, whereas the increases induced by thrombin and PAF were only partially inhibited. Agonists increased [Ca2+]i through release from internal stores and sustained Ca2+ influx. Thrombin stimulated Mn2+ influx, which was blocked by Ni2+. Diltiazem, isradipine, gramicidin and 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride (SK&F 96365) did not affect agonist-induced rises in [Ca2+]i. HEL cells contained substantial amounts of beta-glucuronidase which, however, could not be released, and they did not aggregate or generate superoxide. Our data suggest that: (1) HEL cells possess nucleotide receptors with properties similar to those of phagocytes; (2) they possess receptors for PGE2 and PGI2, and PGE1 is an agonist at both receptors; (3) agonist-induced increases in [Ca2+]i are mediated through pertussis toxin-sensitive as well as -insensitive signal transduction pathways; and (4) agonists increase [Ca2+]i by mobilization from internal stores and influx from the extracellular space through cation channels with properties similar to those of phagocytes and platelets.
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PMID:Receptor-mediated increases in cytosolic Ca2+ in the human erythroleukaemia cell line involve pertussis toxin-sensitive and -insensitive pathways. 131 May 89

1. We have examined the effects of neuropeptide Y (NPY) on synaptic transmission and [Ca2+]i signals in rat hippocampal neurones grown in culture. [Ca2+]i in individual neurones displayed frequent spontaneous fluctuations often resulting in an elevated plateau [Ca2+]i. These fluctuations were reduced by tetrodotoxin (1 microM) or combinations of the excitatory amino acid antagonists 6-cyano-7-dinitro-quinoxaline (CNQX) (10 microM) and aminophosphonovalerate (APV) (50 microM), indicating that they were the result of glutamatergic transmission occurring between hippocampal neurones. 2. [Ca2+]i fluctuations were also prevented by Ni2+ (200 microM), by the GABAB receptor agonist, baclofen (10 microM) and by NPY (100 nM) or Y2 receptor-selective NPY agonists. Following treatment of cells with pertussis toxin, NPY produced only a brief decrease in [Ca2+]i fluctuations which rapidly recovered. 3. Perfusion of hippocampal neurones with 50 mM K+ produced a large rapid increase in [Ca2+]i. This increase was slightly reduced by NPY or by a combination of CNQX and APV. The effects of CNQX/APV occluded those of NPY. NPY had no effect on Ba2+ currents measured in hippocampal neurones under whole cell voltage-clamp even in the presence of intracellular GTP-gamma-S. On the other hand, Ba2+ currents were reduced by both Cd2+ (200 microM) and baclofen (10 microM). 4. Current clamp recordings from hippocampal neurones demonstrated the occurrence of spontaneous e.p.s.ps and action potential firing which were accompanied by increases in [Ca2+]i. This spontaneous activity and the accompanying [Ca2+]i signals were prevented by application of NPY (100 nM). When hippocampal neurones were induced to fire trains of action potentials in the absence of synaptic transmission, these were accompanied by an increase in cell soma [Ca2+]j. NPY (100 nM) had no effect on these cell soma [Ca2+], signals. NPY (100 nM) also had no effect on inward currents generated in hippocampal neurones by micropipette application of glutamate (50 microM).5. Thus, NPY is able to abolish excitatory neurotransmission in hippocampal cultures through a pertussis toxin-sensitive mechanism. However, no effect of NPY on Ca2+ influx into the cell soma of these hippocampal neurones could be discerned. These results are consistent with a localized presynaptic inhibitory effect of NPY on glutamate release in hippocampal neurones in culture.
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PMID:Investigations into neuropeptide Y-mediated presynaptic inhibition in cultured hippocampal neurones of the rat. 135 89

Previous work indicates that antagonists of the L-type voltage-dependent Ca2+ channel (VDCC) prevent the Ca(i) increase in mammalian sperm that is promoted by incubation in alkaline, K(+)-based media. Here, were provide additional evidence that sperm possess VDCC and show that their activation is required for the Ca2+ entry that mediates acrosomal exocytosis in both the presence and the absence of egg agonists. Specifically, we report that: (1) Sperm membrane potential changes, Ca(i) elevation, and acrosomal exocytosis have similar K+ dose dependencies, consistent with a characteristic requirement of a large depolarization for activation of the sperm VDCC; (2) High affinity binding sites (Kd approximately 0.35 +/- 0.03 and 0.45 +/- 0.06 nM; Bmax = 16.0 +/- 1.4 and 5.8 +/- 0.8 fmole/mg protein) for the VDCC antagonist, PN200-110, respectively, are present in membrane preparations from sperm of the ram and bull; (3) PN200-110 and the other VDCC antagonists nitrendipine, nisoldipine, verapamil, diltiazem, Ni2+, or Co2+ inhibit (IC50 = 0.1, 0.4, 0.6, 0.8, 1.0, 60, and 110 microM, respectively) the acrosomal exocytosis produced by combined elevation of pH0 and membrane depolarization; (4) Exocytosis induced by the ZP3 agonist of the mammalian egg also is inhibited by VDCC antagonists with similar dose dependencies; (5) Depolarizing treatments that presumably activate the sperm VDCC bypass the blockade of ZP3-induced exocytosis imposed by pertussis toxin. These results indicate that activation of the sperm VDCC is sufficient to induce sperm acrosomal exocytosis and that VDCC activation is necessary in the ZP3 signal transduction pathway. They also indicate that the presumed G-protein targets of pertussis toxin probably produce a required but indirect activation of the putative sperm VDCC. Possible intervening events include alteration of the voltage sensitivity of the VDCC, membrane depolarization, or both. We suggest that the depolarization-induced acrosome reaction may provide a useful system to investigate subsequent events in the exocytotic process.
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PMID:Activation of voltage-dependent calcium channels of mammalian sperm is required for zona pellucida-induced acrosomal exocytosis. 137 59

G-proteins are important mediators of hormonal inhibition of insulin secretion. To characterize the pertussis toxin-sensitive substrates present in HIT cell membranes, we performed immunoblots with specific antisera and found evidence for the presence of Gi alpha 1, Gi alpha 2, Gi alpha 3, and three forms of Go alpha. We observed that pertussis toxin-sensitive substrates mediate all of the effects of SRIF, and a major portion of the effects of EPI, on insulin secretion from rat islets during static incubations. These results agree with our previously reported studies examining phasic glucose-induced insulin secretion from HIT cells. To ascertain whether inhibition of adenylate cyclase, presumably involving coupling of the catalytic subunit to Gi, may be a common mechanism for both hormones, we studied the effects of 8-bromo-cyclic AMP and found that this agent partially prevented the inhibitory effects of both hormones. We also observed that the inhibitory effects of SRIF and EPI on insulin were nonadditive, that both hormones were additive to nickel chloride during inhibition of insulin release, and that they noncompetitively inhibited glipizide-induced insulin secretion through pertussis toxin-sensitive mechanisms. Together, these results suggest that both hormones exert their effects on insulin secretion at multiple G-protein-regulated sites including adenylate cyclase and sites distal to the glipizide-binding site on the KATP channel.
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PMID:G-proteins and hormonal inhibition of insulin secretion from HIT-T15 cells and isolated rat islets. 138 67

Bradykinin (BK) induced [3H]norepinephrine [( 3H]NE) release and phosphatidylinositol turnover were investigated in PC12 cells. Induction of [3H]NE release by BK is mediated by activation of BK-B2-receptors, as determined using type specific BK receptor antagonists. BK induces [3H]NE release with a half maximal effective concentration of 30 +/- 0.5 nM, and reaches maximal net fractional release of 9.0 +/- 1% with 200 nM BK. The BK-induced release is Ca2+ dependent, reaching maximal release at 1.0 mM Ca2+, is pertussis toxin insensitive (1 microgram/ml), slightly increased by a dibutyryl cAMP (1 mM) and not affected by inhibitors of the cyclooxygenase or lipoxygenase pathways. Voltage-sensitive Ca2+ channel blockers, verapamil (10 microM), nifedipine (10 microM), and omega-conotoxin (CgTx 10 nM), do not block the BK-induced release. However, a considerable inhibitory effect was obtained by divalent cations Co2+ (ED50 = 0.2 mM) and Ni2+ (ED50(2)+ = 1 mM). These results indicate the involvement of a Ca2+ channel in the BK-mediated release which is different from the L- or N-type voltage sensitive calcium channels. Whereas [Ca2+]ex is essential for the BK-induction of catecholamine release, the rise in level of InsP's induced by BK in the presence or in the absence of [Ca2+]ex is similar up to concentration of 1 microM. This indicates that the rise in InsP's induced by BK is not sufficient to cause neurotransmitter release. Moreover, subsequent addition of Ca2+ to BK-stimulated cells in Ca(2+)-free medium yields no release. Hence, no activity triggered by BK alone could be further stimulated by Ca2+ for induction of release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The bradykinin receptor--a putative receptor-operated channel in PC12 cells: studies of neurotransmitter release and inositol phosphate accumulation. 164 55

1. Intracellular and whole-cell recordings were made from primary cultures of rat intermediate pituitary cells; beta-endorphin secretion was also measured by radioimmunoassay. The effects of dopamine receptor activation on hormone secretion, calcium currents and resting potassium conductance were compared. 2. Spontaneous sodium-dependent action potentials occurred in 82% of cells recorded with intracellular microelectrodes and 64% of cells recorded with whole-cell patch electrodes; the same proportion of cells showed spontaneous calcium-dependent depolarizations in the presence of tetrodotoxin. 3. Calcium currents recorded from holding potentials of -90 or -70 mV showed transient and sustained components, both of which activated at -40 mV and had similar current-voltage relations. Bay K 8644 (1 microM) increased both components by about 130% while nifedipine (1-10 microM) decreased them by a maximum of 30%. Nickel (500 microM) inhibited transient and sustained components by 68 and 50%; cadmium (100 microM) abolished the current. omega-Conotoxin (1 microM) reversibly inhibited the transient component by 26%. 4. The dopamine D2 receptor agonist, quinpirole (0.1-10 microM) inhibited transient and sustained components in all cells by a maximum of 40 and 25% respectively. Quinpirole did not alter the time course of the current. 5. Quinpirole (1-100 nM) hyperpolarized 90% of cells from which intracellular recordings were made and 55% of cells recorded from with whole-cell patch pipettes. Maximum hyperpolarization of 16 +/- 4 mV from a resting potential of -44 +/- 5 mV was observed with 100 nM-quinpirole; concentration producing half-maximal effect was 3 nM. The hyperpolarization resulted from an increase in potassium conductance. 6. Quinpirole (1-100 nM) decreased basal beta-endorphin secretion by 55% and abolished secretion stimulated by Bay K 8644 or isoprenaline; concentrations producing half-maximal inhibitions were 5-10 nM. Tetrodotoxin (1 microM), nifedipine (1 microM), nickel (500 microM) and cadmium (100 microM) did not alter basal or stimulated secretion although higher concentrations of cadmium did inhibit stimulated hormone release. 7. Pertussis toxin pre-treatment prevented all actions of quinpirole. 8. Thus, concentrations of quinpirole that abolished stimulated hormone secretion did not alter calcium currents; conversely, concentrations of calcium channel blockers that partially or completely inhibited calcium currents did not alter basal or stimulated secretion. These results may indicate that calcium influx through the voltage-dependent calcium channels measured in these experiments does not contribute significantly to hormone release from melanotrophs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dopamine actions on calcium currents, potassium currents and hormone release in rat melanotrophs. 171 75

Recombinant monocyte-chemotactic and activating factor (rMCAF; alternative acronyms MCP-1, TDCF, human JE) induced migration of human monocytes across polycarbonate or nitrocellulose filters. Maximal induction of migration was observed at a concentration of 10 ng/ml (10(-9) M). Checkerboard analysis revealed that rMCAF elicited true gradient-dependent chemotactic migration, although a gradient independent chemokinetic effect was observed at low concentrations (1-5 ng/ml). rMCAF caused a rapid (less than 5 s) and transient (approximately 1.5 min) increase of free cytosolic Ca2+ ions, as assessed by the fura-2 probe. No Ca2+ increase was detected in neutrophils or lymphocytes stimulated by rMCAF. Studies conducted in the absence of extracellular Ca2+ or in the presence of Ni2+ (an inhibitor of Ca2+ influx) suggested that the increase of intracellular Ca2+ induced by rMCAF is dependent on the influx of extracellular Ca2+ through plasma membrane channels. Bordetella pertussis toxin inhibited the intracellular Ca2+ elevation and chemotaxis caused by rMCAF. The possible involvement of Ca(2+)-dependent protein kinases in rMCAF signaling pathway(s) was explored using inhibitors. Inhibitors of GMP-dependent kinase and myosin L chain kinase had no effect on rMCAF-induced monocyte migration. In contrast, protein kinase C/cAMP-dependent kinase inhibitors (such as, C-I, H-7, HA-1004, KT5720, and Staurosporine) markedly decreased rMCAF induced chemotaxis suggesting the involvement of a serine/threonine protein kinase, possibly protein kinase C, in rMCAF signaling pathway.
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PMID:The signal transduction pathway involved in the migration induced by a monocyte chemotactic cytokine. 191 57

We measured changes in the molar concentration of cytosolic Ca2+ ([Ca2+]i) in individual astrocytes in culture produced by the glutamate analog quisqualate (QA) and related substances by using fura-2 digital fluorescence microscopy. In cells cultured from the cortex, hippocampus, and cerebellum, the QA analog alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA; 10 microM) produced a slow increase in [Ca2+]i that was modest in amplitude (approximately 200 nM). These effects were completely abolished by 10 microM 6-nitro-7-cyano-quinoxaline-2,3-dione (CNQX). In cerebellar astrocytes, similar effects were produced by QA. However, in cortical and hippocampal astrocytes, the response to QA was much more complex. In these cells, QA produced an initial [Ca2+]i spike that was followed by a sustained influx of Ca2+ ("plateau"). In the absence of extracellular Ca2+, this plateau was abolished but the spike remained. CNQX did not block the spike and only slightly reduced the size of the plateau in some cells. Ni2+ (10 microM) but not nimodipine (10 microM) reduced the amplitude of the plateau. Pretreatment with 100 nM phorbol 12-myristate 13-acetate for 15 min abolished the spike but not the plateau portion of the QA response. Treatment with pertussis toxin at 250 ng/ml for 12-16 hr failed to alter the response. In some instances, the latency of the QA response differed considerably for individual cells in a group. It appeared that the response began in one cell and then spread to neighboring cells. Thus, QA appears to trigger a complex response in some astrocytes consisting of Ca2+ mobilization from intracellular stores and also Ca2+ influx resulting from the activation of AMPA-sensitive and -insensitive pathways.
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PMID:Glutamate receptors activate Ca2+ mobilization and Ca2+ influx into astrocytes. 197 Jun 37

1. Somatotrophs were obtained from rat pituitary glands after dissociation, separation and enrichment on a continuous gradient of bovine serum albumin at unit gravity. Somatotrophs were enriched up to 85% in the heavy fractions (F8 and F9). 2. After identification by reverse hemolytic plaque assay, patch-clamp recording in the whole-cell mode was performed on somatotrophs. 3. Under voltage-clamp conditions, two types of Ca2+ currents were recorded. From a holding potential of -70 mV, depolarizing voltage steps to potentials more positive than -50 mV activated a current which rapidly inactivated and which was very sensitive to Ni2+ but not to Cd2+. This current corresponds to T-type current. Depolarizing steps to potentials more positive than -30 mV from a holding potential of -40 mV triggered a current which slowly inactivated and which was very sensitive to Cd2+ but not to Ni2+. This current corresponds to L-type current. 4. Application of somatostatin to the bath solution (10 nM) markedly reduced the amplitudes of both T- and L-type currents. Somatostatin decreased the conductance of L-type current without modifying its time- and voltage-dependent inactivation but its activation was not affected. However, somatostatin decreased the conductance of T-type currents, and also accelerated its time-dependent inactivation. Half-inactivation voltage of T-type current was shifted from -52 to -63 mV by somatostatin but no change was obtained in the current activation curve. 5. All these modifications in Ca2+ currents were abolished by a pre-treatment of the cultures with pertussis toxin (100 ng/ml, for 10 h). This pre-treatment also blocked the inhibitory effect of somatostatin on high-K(+)-stimulated growth hormone release. 6. Our results show that somatostatin acts on somatotrophs by attenuating the voltage-dependent Ca2+ currents. These effects may contribute to a somatostatin-induced reduction in [Ca2+]i and the subsequent decline in growth hormone release.
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PMID:Two types of voltage-dependent calcium current in rat somatotrophs are reduced by somatostatin. 197 2


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