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

Sprague Dawley rats were sensitized with 20 microgram or 100 mg egg albumin (using pertussis vaccine as adjuvant). Mast cells isolated from the former group of animals showed a higher degree of histamine release upon challenge in vitro with egg albumin than those from the latter group. Using the lower amount of antigen for immunization mast cells from Hooded Lister rats showed an even higher degree of histamine release induced by antigen. An increased antigen-induced histamine release was associated with an increased spontaneous and phosphatidylserine-induced histamine release. Histamine release induced by phosphatidylserine was found to be specific in so far as it was calcium dependent and theophylline-inhibited. The basal level of cyclic AMP in mast cells was significantly depressed by sensitization. There was a relationship between the cyclic AMP/cyclic GMP ratio and the degree of spontaneous, phosphatidylserine-induced and anaphylactic histamine release. The results suggest that sensitization induces an increased release of histamine not only to the specific antigenic stimulus but also to more unspecific stimuli. Concomitantly there is a fall in the cyclic AMP/cyclic GMP ratio. The relationship between these two phenomena is discussed.
 ...
PMID:Effect of sensitization on spontaneous and phosphatidylserine-induced histamine release and on cyclic AMP and GMP levels in isolated rat mast cells. 9 6

The mechanism whereby "islet-activating protein" (IAP) purified from the culture medium of Bordetella pertussis potentiates insulin secretion was studied by experiments in vitro with islets of rats once injected with IAP (0.5 micrograms/100 g body weight, 3 days before killing) or with islets that had been exposed to IAP (0.1 to 100 ng/ml) for 24 h. The IAP treatment markedly enhanced insulin secretory responses and cAMP accumulation in islets, facilitated the efflux of 45Ca through the cell membrane, and abolished the alpha-adrenergic action of epinephrine (and somatostatin) to inhibit glucose-induced insulin release, cAMP accumulation, and 45Ca uptake. These effects of the IAP treatment were reduced when islets were incubated in a low calcium medium. Based on these results, it was concluded that IAP interacts directly but slowly with the islet B cell in such a manner as to render more calcium available to the stimulus-secretion coupling mechanism as a result of sustained activation of native calcium ionophores on the cell membrane.
 ...
PMID:Islet-activating protein. Enhanced insulin secretion and cyclic AMP accumulation in pancreatic islets due to activation of native calcium ionophores. 21 76

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.
 ...
PMID:Modulation of (+)-[3H]pentazocine binding to guinea pig cerebellum by divalent cations. 127 78

TRH stimulates a biphasic increase in intracellular free calcium ion, [Ca2+]i. Cells stably transfected with TRH receptor cDNA were used to compare the response in lines with and without L type voltage-gated calcium channels. Rat pituitary GH-Y cells that do not normally express TRH receptors, rat glial C6 cells, and human epithelial Hela cells were transfected with mouse TRH receptor cDNA. All lines bound similar amounts of [3H][N3-Me-His2]TRH with identical affinities (dissociation constant = 1.5 nM). Both pituitary lines expressed L type voltage-gated calcium channels; depolarization with high K+ increased 45Ca2+ uptake 20- to 25-fold and [Ca2+]i 12- to 14-fold. C6 and Hela cells, in contrast, appeared to have no L channel activity. GH4C1 cells responded to TRH with a calcium spike (6-fold) followed by a sustained second phase. When TRH was added after 100 nM nimodipine, an L channel blocker, the initial calcium burst was unaffected but the second phase was abolished. GH-Y cells transfected with TRH receptor cDNA responded to TRH with a 6-fold [Ca2+]i spike followed by a plateau phase (>8 min) in which [Ca2+]i remained elevated or increased. Nimodipine did not alter the peak TRH response or resting [Ca2+]i but reduced the sustained phase, which was eliminated by chelation of extracellular Ca2+. In the transfected glial C6 and Hela cells without calcium channels, TRH evoked transient, monophasic 7- to 9-fold increases in [Ca2+]i, and [Ca2+]i returned to resting levels within 3 min. Thapsigargin stimulated a gradual, large increase in [Ca2+]i in transfected C6 cells, and subsequent addition of TRH caused no further rise. Removal of extracellular Ca2+ from transfected C6 cells shortened the [Ca2+]i responses to TRH, to endothelin 1, and to thapsigargin. The TRH responses were pertussis toxin-insensitive. In summary, TRH can generate a calcium spike in pituitary, C6, and Hela cells transfected with TRH receptor cDNA, but the plateau phase of the [Ca2+]i response is not observed when the receptor is expressed in a cell line without L channel activity.
 ...
PMID:Characterization of the calcium response to thyrotropin-releasing hormone (TRH) in cells transfected with TRH receptor complementary DNA: importance of voltage-sensitive calcium channels. 127 82

The regulation of Cl- channels in human myoballs by G proteins was studied using whole-cell and inside-out patch recordings. After perfusion of the cell with 0.1 mM GTP[gamma S], the specific Cl- conductance, GCl, at standard resting potential (-85 mV) was increased from 5.9 microS/cm2 to 103 microS/cm2, and the kinetics upon stepping the potential to positive values was changed from an activating current with very slow inactivation to a fast inactivating current with no potential-dependent activation. These effects were not affected by the simultaneous blockade of several signal cascades involving G proteins. Addition of the protein kinase blockers PKI (25 microM), H8 (10 microM), or of the phospholipase-A2-blocking agent quinacrine (10 microM), had not much influence on these GTP[gamma S] effects. Buffering of the intracellular Ca2+ concentration (0.1 microM) or addition of the Ca2+/calmodulin antagonist trifluoperazine (50 microM) was also without effect. Pre-incubation of the cells with pertussis toxin or with cholera toxin did not change GCl. In excised inside-out patches voltage-clamped at -85 mV, application of GTP[gamma S] influenced the "intermediate" Cl- channel, the Cl- channel type having the highest density in these cells, by increasing the number of transitions in a half-conductance state. The probability of the channel being in one of the two conducting states rose from 0.015 to 0.67, and the kinetics of the single-channel currents was changed so that, on average, it was similar to the whole-cell current kinetics seen after application of GTP[gamma S]. It is concluded that a G protein is directly interacting with these channels.
 ...
PMID:Chloride channels in cultured human skeletal muscle are regulated by G proteins. 127 15

A PC12 cell clone that responds to ATP with polyphosphoinositide hydrolysis and with a marked, biphasic intracellular free Ca2+ concentration ([Ca2+]i) response (composed by release from intracellular stores accompanied by stimulated influx from the medium), was pretreated with pertussis toxin. In the pretreated cells the responses induced by ATP were differently modified. Polyphosphoinositide hydrolysis and Ca2+ release were moderately inhibited whereas Ca2+ influx was enhanced. Pharmacological experiments revealed the influx enhancement to be sustained by neither voltage-gated nor second messenger-operated Ca2+ channels. Rather, a channel of the receptor-operated type activated by ATP (P2w receptor) appears to work under the negative control of a pertussis toxin-sensitive G protein, acting presumably by direct interaction with the channel in the plane of the plasma membrane.
 ...
PMID:ATP-induced Ca2+ influx is regulated via a pertussis toxin-sensitive mechanism in a PC12 cell clone. 128 Jan 32

In the human erythroleukemia cell line, HEL, prostaglandin E2 (PGE2) and the stable prostacyclin analogue, iloprost, increase cytosolic Ca2+ concentration ([Ca2+]i) via pertussis toxin-sensitive and -insensitive pathways. Unlike iloprost, the stable prostacyclin analogue cicaprost (ZK 96480), is devoid of agonistic properties at prostaglandin E2 receptors. We compared the effects of cicaprost, iloprost and PGE2 on [Ca2+]i in HEL cells. Cicaprost, iloprost and PGE2 were similarly potent to increase [Ca2+]i in HEL cells. However, unlike the effects of PGE2, those of the prostacyclin analogues were not inhibited by pertussis toxin. The prostaglandins studied increased [Ca2+]i through both mobilization from internal stores and Ca2+ influx from the extracellular space. Prostacyclin analogue- and PGE2-induced rises in [Ca2+]i were desensitized in a homologous manner. Additionally, there was cross-desensitization between cicaprost and iloprost, but not between the prostacyclin analogues and PGE2. Our data suggest that in HEL cells (i) cicaprost and iloprost act through prostacyclin receptors and (ii) that these receptors couple to pertussis toxin-insensitive heterotrimeric regulatory guanine nucleotide-binding proteins, (iii) resulting in an increase in [Ca2+]i by Ca2+ mobilization from internal stores and sustained influx.
 ...
PMID:The prostacyclin analogues, cicaprost and iloprost, increase cytosolic Ca2+ concentration in the human erythroleukemia cell line, HEL, via pertussis toxin-insensitive G-proteins. 128 Apr 55

In human neutrophils, the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) induces increases in the intracellular free Ca2+ concentration ([Ca2+]i) with subsequent activation of beta-glucuronidase release and superoxide (O2-) production. Results from several laboratories suggest that the increase in [Ca2+]i is due to activation of non-selective cation (NSC) channels. We studied the biophysical characteristics, pharmacological modulation and functional role of NSC channels in dibutyryl cyclic AMP (Bt2cAMP)-differentiated HL-60 cells. fMLP increased [Ca2+]i by release of Ca2+ from intracellular stores and influx of Ca2+ from the extracellular space. fMLP also induced Mn2+ influx. Ca2+ and Mn2+ influxes were inhibited by 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride (SK&F 96365). Under whole-cell voltage-clamp conditions, fMLP and ATP (a purinoceptor agonist) activated inward currents characterized by a linear current-voltage relationship and a reversal potential near 0 mV. NSC channels were substantially more permeable to Na+ than to Ca2+. SK&F 96365 inhibited fMLP- and ATP-stimulated currents with a half-maximal effect at about 3 microM. Pertussis toxin prevented stimulation by fMLP of NSC currents and reduced ATP-stimulated currents by about 80%. Intracellular application of the stable GDP analogue, guanosine 5'-O-[2-thio]diphosphate, completely blocked stimulation by agonists of NSC currents. In excised inside-out patches, single channel openings with an amplitude of 0.24 pA were observed in the presence of fMLP and the GTP analogue, guanosine 5'-O-[3-thio]triphosphate. The bath solution contained neither Ca2+ nor ATP. The current/voltage relationship was linear with a conductance of 4-5 pS and reversed at about 0 mV. fMLP-induced beta-glucuronidase release and O2- production were substantially reduced by replacement of extracellular CaCl2 or NaCl by ethylenebis(oxyethylenenitrilo)tetra-acetic acid and choline chloride respectively. In the absence of Ca2+ and Na+, fMLP was ineffective. SK&F 96365 inhibited fMLP-induced beta-glucuronidase release and O2- production in the presence of both Ca2+ and Na+, and in the presence of Ca2+ or Na+ alone. NaCl (25-50 mM) enhanced the basal and absolute extent of fMLP-stimulated GTP hydrolysis of heterotrimeric regulatory G-proteins in HL-60 membranes. The order of effectiveness of salts in enhancing GTP hydrolysis was LiCl > KCl > NaCl > choline chloride.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Formyl peptides and ATP stimulate Ca2+ and Na+ inward currents through non-selective cation channels via G-proteins in dibutyryl cyclic AMP-differentiated HL-60 cells. Involvement of Ca2+ and Na+ in the activation of beta-glucuronidase release and superoxide production. 128 79

The effect of the neuropeptides substance P, neurokinin A and alpha-calcitonin gene-related peptide (CGRP) on human neutrophil granulocytes was investigated. Substance P induced secondary granule secretion at a concentration of 100 microM. CGRP induced a significant secretory response at 10 microM and thus appeared to be about 10 times more potent than substance P. Calcitonin and a fragment of CGRP, CGRP(8-37), had no effect on neutrophil degranulation. The chemotactic peptide antagonist BOC-MLP (100 microM) inhibited lactoferrin secretion mediated both by CGRP and chemotactic peptide FMLP almost completely, while secretion in response to tumour necrosis factor (TNF) was unaffected. Results from receptor binding studies showed that CGRP and N-formyl-methionyl-leucyl-phenylalanine (FMLP) do not compete for binding. This indicates that CGRP does not exert its effects by binding to the chemotactic peptide receptor. CGRP induced a rapid increase in the cytosolic-free calcium concentration and this increase was not, unlike that induced by FMLP, abolished by preincubation of the cells with pertussis toxin (1000 ng/ml). Therefore CGRP signal transduction in neutrophils appears to involve rapid changes in the cytosolic-free calcium concentration but not a pertussis toxin-sensitive G-protein. In summary, this is the first report to show that CGRP can directly activate neutrophil granulocytes, and this probably occurs via a cell surface receptor which is distinct from that of FMLP although both the CGRP and FMLP-mediated effects can be blocked by BOC-MLP.
 ...
PMID:Calcitonin gene-related peptide (CGRP) activates human neutrophils--inhibition by chemotactic peptide antagonist BOC-MLP. 128 94

1. In order to determine the intracellular mechanisms by which galanin induces contraction of isolated smooth muscle cells from pig ileum, we examined the effects of external Ca2+, relaxing agents, pertussis toxin and forskolin on the galanin-induced contraction and compared these effects to those observed on the cholecystokinin derivative CCK8-induced contraction. 2. Galanin induced a concentration-dependent cell contraction. The maximal contraction (24.5 +/- 2.1% of the length of resting cells) was observed at 1 nM of galanin. When cells were incubated in the simultaneous presence of concentrations of galanin (10 fM) and CCK8 (1 pM) which were ineffective alone, or galanin (10 fM) and acetylcholine (100 pM), a synergistic action was observed corresponding to a submaximal contraction. 3. Incubation of cells in Ca(2+)-free medium caused a significant decrease in galanin- but not in CCK-induced contraction. Nifedipine, a Ca2+ channel blocker, provoked a concentration-dependent inhibition of galanin-induced contraction while it had no effect on the contraction induced by CCK8. 4. Vasoactive intestinal polypeptide (VIP) and isoprenaline, known to induce cell relaxation through an increase in intracellular cAMP level, inhibited CCK-induced cell contraction at concentrations ranging from 1 pM to 1 microM but failed to inhibit cell contraction induced by galanin. 5. When cells were pre-incubated for 3 h in the presence of 200 ng/ml of pertussis toxin, the contraction induced by galanin was abolished while the CCK-induced contraction remained unchanged. On the contrary, 10 microM forskolin abolished the contraction induced by 10 nM CCK but had no effect on galanin-induced contraction. 6. These results indicate that galanin induces a concentration-dependent contraction of pig ileum smooth muscle by a direct myogenic effect. This effect of galanin involves the activation of a pertussis toxin-sensitive G protein, which results in an influx of Ca2+ into the cell. This intracellular pathway is insensitive to the relaxing effect of cAMP.
 ...
PMID:Intracellular pathways triggered by galanin to induce contraction of pig ileum smooth muscle cells. 128 68


1 2 3 4 5 6 7 8 9 10 Next >>