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. Inhibitory modualtion of the three Ca2+ channel current components by neurotransmitters was studied using the whole-cell patch-clamp method in a mammalian cell line, NG108-15. 2. In cells differentiated with dibutyryl cyclic AMP, both the low-voltage-activated current (ILVA) and omega CgTX-sensitive high-voltage-activated current (I omega CgTX) could be inhibited by [D-phen2, D-phen5]enkephalin, acetylcholine and noradrenaline. In contrast, differentiation with prostaglandin E1 and theophylline eliminated the agonist-induced inhibition of ILVA, but enhanced that of I omega CgTX. The DHP-sensitive high-voltage-activated current was unaffected by the transmitters in most of the cells. 3. The inhibition was prevented by pre-treatment of cells with pertussis toxin, suggesting involvement of a G-protein. Long treatment of the cells with phorbol ester did not prevent the inhibition. 4. The inhibition was always partial: the maximal inhibition was 40% for ILVA and 70% for I omega CgTX. 5. The inhibition of ILVA and I omega CgTX was relieved during depolarization. Half-maximal relief of inhibition of I omega CgTX was attained at 0 mV, irrespective of agonist concentration. 6. The kinetics of removal and re-establishment of inhibition were voltage dependent. Both processes were single exponentials and had identical time constants at a given membrane potential. Time constants were 124 ms at -40 mV, 160 ms at 0 mV and 8 ms at 60 mV, at any agonist concentration. 7. Time courses of tail currents were unaltered by the inhibition. 8. The inhibition of the omega CgTX-sensitive Ca2+ channel can be described as a shift in gating modes; with an additional voltage-dependent gating state activated by the agonists. The voltage-dependent properties of this modulation allow inhibition of Ca2+ channel to be overcome by high-frequency trains of action potentials.
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PMID:Voltage- and time-dependent inhibition of neuronal calcium channels by a GTP-binding protein in a mammalian cell line. 135 Jun 37

Effects of alpha 2-adrenoceptor agonists on whole-cell Ca2+ currents and 3H-noradrenaline release were investigated by applying the patch-clamp technique and electrical field stimulation to cultured embryonic chick sympathetic neurons. A 24-h exposure of the sympathetic neurons to pertussis toxin (100 ng/ml) abolished both the alpha 2-adrenoceptor-mediated inhibition of Ca2+ currents and the modulation of noradrenaline release caused by noradrenaline (1 mumol/l; in the presence of 10 mumol/l cocaine) or the alpha 2-adrenoceptor agonists 5-bromo-6-(2-imidazolin-2- ylamino)quinoxaline (UK 14,304, 10 mumol/l) and clonidine (10 mumol/l). These results suggest that the alpha 2-autoreceptor-mediated inhibition of noradrenaline release from chick sympathetic neurons operates through the modulation of Ca2+ channels via pertussis-toxin-sensitive GTP-binding-proteins.
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PMID:Pertussis toxin abolishes the inhibition of Ca2+ currents and of noradrenaline release via alpha 2-adrenoceptors in chick sympathetic neurons. 135 37

1. The identity of the G-proteins involved in prejunctional alpha 2-adrenoceptor signal transduction in mouse atria was examined by use of the G-protein inactivators N-ethylmaleimide and pertussis toxin. 2. The alpha 2-adrenoceptor partial agonist clonidine (0.03 microM) inhibited the electrical stimulation-induced (S-I) outflow of radioactivity from mouse atria which were incubated with [3H]-noradrenaline and stimulated at 5 Hz. The partial alpha 2-adrenoceptor agonist St 363 (10 microM) inhibited the S-I outflow of radioactivity at the lower stimulation frequency of 2.5 Hz. The inhibitory effects of these compounds were not altered in mice pretreated with pertussis toxin (1.5 micrograms, i.v.). 3. The alpha 2-adrenoceptor antagonist, idazoxan (0.1 microM), increased the S-I outflow of radioactivity from mouse atria stimulated at 5 Hz, and this effect was not altered in atria from mice pretreated with pertussis toxin. 4. The inhibitory effects of clonidine and St 363 and the facilitatory effect of idazoxan on the S-I outflow of radioactivity from mouse atria were significantly less in atria incubated with N-ethylmaleimide (NEM, 3 microM) for 60 min before the [3H]-noradrenaline incubation. 5. The results suggest that prejunctional alpha 2-adrenoceptors in mouse atria function through G-proteins which are NEM-sensitive, but pertussis toxin insensitive.
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PMID:Prejunctional alpha 2-adrenoceptors in mouse atria function through G-proteins which are sensitive to N-ethylmaleimide, but not pertussis toxin. 135 69

1. Whole-cell calcium currents of bullfrog sympathetic neurones were partially inhibited by noradrenaline (NA), chicken-II-luteinizing hormone-releasing hormone (LHRH), muscarine, ATP, substance P, or intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate)(GTP-gamma-S) or aluminium fluoride. These agents had similar effects on the activation kinetics of calcium current. 2. The amplitude of the LHRH effect varied from cell to cell. This did not correlate with cell size or the time of whole-cell dialysis. 3. The response to LHRH desensitized rapidly. Desensitization to LHRH did not affect inhibition by NA, ATP or substance P. 4. The effects of LHRH and NA were partially additive. 5. Cells dialysed with GTP-gamma-S still responded to NA or LHRH. However, NA or LHRH inhibited a smaller fraction of the calcium current than usual, and second applications of the same transmitter to GTP-gamma-S-dialysed cells were ineffective. 6. In GTP-gamma-S-dialysed cells, application of LHRH occluded the response to NA, but LHRH was still effective after application of NA. 7. The effect of GTP-gamma-S decreased during prolonged dialysis. 8. The effect of NA was selectively reduced by intracellular dialysis with the A-protomer of pertussis toxin (PTX), or extracellular pretreatment with high concentrations of whole PTX at room temperature. These treatments had little or no effect on the action of LHRH or ATP. 9. It is concluded that multiple G proteins can produce identical changes in calcium channel gating. The adrenergic receptor preferentially couples to a PTX-sensitive G protein.
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PMID:Calcium current modulation in frog sympathetic neurones: multiple neurotransmitters and G proteins. 135 63

The effects of the high affinity sigma (sigma) ligands 1,3-di(2-tolyl)guanidine (DTG), (+)N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1- ethyl-but-3-en-1-yl-amine hydrochloride (JO-1784), (+)3-[3-hydroxyphenyl]-N-(1-propyl)piperidine hydrochloride [(+)3-PPP] and haloperidol were studied on N-methyl-D-aspartate (NMDA)-evoked release of [3H]noradrenaline (NA) from preloaded hippocampal slices made from Sprague-Dawley rats. The [3H]NA release was evoked once by a 4 min exposure to NMDA, 40 min after the beginning of superfusion with a Mg+(+)-free Krebs' solution. In the absence of any drug, NMDA evoked a concentration-dependent [3H]NA release. Mg++ and EGTA abolished the [3H]NA release induced by NMDA. JO-1784 and (+)3-PPP potentiated in a concentration-dependent manner NMDA-induced [3H]NA release, without affecting the basal outflow. DTG concentration-dependently inhibited the overflow of [3H]NA evoked by NMDA, without affecting the basal efflux. Haloperidol, which did not modify NMDA-evoked [3H]NA release by itself, completely prevented the effects of JO-1784, (+)3-PPP and DTG. In contrast, spiperone, also a potent dopamine receptor antagonist but with low affinity for sigma binding sites, failed to prevent the potentiation of NMDA-evoked release of [3H]NA by JO-1784 and (+)3-PPP. The possible involvement of Gi/o proteins in the modulation by sigma ligands of NMDA-evoked [3H]NA release in the rat hippocampus was also investigated. To this end, Gi/o proteins were inactivated with pertussis toxin (PTX), injected locally 3 to 11 days prior to the experiment or with in vitro preincubation with N-ethylmaleimide (NEM) for 30 min prior the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation by sigma ligands of N-methyl-D-aspartate-induced [3H]noradrenaline release in the rat hippocampus: G-protein dependency. 140 2

Catecholamines have been shown to activate hypothalamic corticotropin-releasing factor-41 (CRF) synthesis and release. In order to study the mechanisms involved, fetal hypothalamic cells were cultured and CRF release was measured by radioimmunoassay. Norepinephrine (NE) induced CRF release in a dose-dependent manner. Further studies were performed with a protein kinase C inhibitor, H-7(1-(5-isoquinolinesulfonyl)-2-methylpiperazine) and a protein kinase A inhibitor, IP-20. NE-stimulated CRF release was reduced by H-7 (5 and 50 microM) in a dose-dependent fashion, while 5 microM IP-20 resulted in a small but significant inhibition. Pretreatment of the cells for 15 h with 20 and 200 nM 12-O-tetradecanoylphorbol-13-acetate, which down-regulates protein kinase C activity, blocked the release of CRF in response to NE (1 microM), further supporting protein kinase C as a mediator for NE-activated CRF release. Pretreatment with 50 and 500 ng/ml pertussis toxin (15 h) resulted in a dose-dependent inhibition of NE-activated CRF release. Both dexamethasone and aldosterone at the concentrations of 1 microM reduced NE-induced CRF release. These results suggest that CRF can be released from hypothalamic neurons in response to NE through both protein kinase C- and protein kinase A-dependent mechanisms, and that pertussis toxin-sensitive G-proteins are also involved in this response. Furthermore, glucocorticoids and mineralocorticoids can reduce NE-activated CRF release from cultured hypothalamic cells.
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PMID:Mechanisms of norepinephrine mediated corticotropin-releasing factor-41 release from cultured fetal hypothalamic cells. 148 3

Histamine activation of H1 receptors stimulates 3H release from cultured bovine adrenal chromaffin cells preloaded with [3H]noradrenaline. The initial (1-min) release induced by a high concentration of histamine was unaffected by the removal of extracellular Ca2+, whereas the more sustained response (10 min) was largely inhibited. In contrast, release induced by nicotine was dependent on extracellular Ca2+ at all times. The protein kinase inhibitor staurosporine inhibited both the initial and sustained (10-min) phases of histamine-induced release (IC50 in the region of 200 nM) but was ineffective against a direct depolarizing stimulus (56 mM K+). In contrast, the calmodulin antagonist trifluoperazine was equally effective against both stimuli. These data indicate that although a staurosporine-sensitive event (perhaps involving protein kinase C) is essential for coupling histamine receptor activation to the release processes, it is not essential for exocytosis itself. A further distinction between histamine- and depolarization-induced release was demonstrated by the differential effect of the guanine nucleotide-binding protein inhibitor pertussis toxin. Pretreatment with pertussis toxin (0.1 microgram/ml for 16 h) enhanced depolarization-induced release by approximately 1.5-fold. This pertussis toxin pretreatment was, however, approximately twofold as effective in potentiating histamine-evoked release. Thus, the characteristics of the histaminergic response are distinct from those of a depolarizing stimulus, perhaps indicating the involvement of different mechanisms in the release process.
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PMID:Characterization of histamine-induced catecholamine secretion from bovine adrenal medullary chromaffin cells. 156 Feb 21

Treatment of cultured rat cardiomyocytes in serum-free medium for 48 h with recombinant human tumor necrosis factor alpha (TNF alpha) led to a concentration-dependent increase in the level of membrane-inhibitory guanine nucleotide-binding protein (Gi) alpha-subunits and in pertussis toxin-catalyzed [32P]ADP ribosylation of 40 kDa proteins. Both Gi alpha protein subtypes present in rat cardiac myocyte membranes, Gi alpha 40 and Gi alpha 41, were up-regulated by the cytokine, with the maximal increase occurring at 10 U/ml TNF alpha. In contrast to noradrenaline exposure, which causes a similar, but apparently exclusive, increase in alpha i-subunits, treatment with TNF alpha in addition increased the level of membrane G protein beta 36-subunits. Furthermore, while noradrenaline exposure led to a decrease in receptor-dependent and -independent adenylyl cyclase activity, treatment of cardiomyocytes with TNF alpha caused a concentration-dependent increase in cyclase responsiveness to either forskolin, guanosine 5'-O-(3-thiotriphosphate) or isoproterenol, even though beta-adrenoceptor density was decreased by TNF alpha. The increase in adenylyl cyclase activity induced by TNF alpha was completely suppressed when the cells were cocultured with noradrenaline, a condition leading to an additive increase in Gi alpha level. The data indicate that the cytokine TNF alpha can potently modulate G protein-mediated signal transduction in rat cardiac myocytes. Although TNF alpha, like noradrenaline, exposure of the cells increased the level of membrane Gi alpha proteins, it did not decrease but rather caused an increase in adenylyl cyclase responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor alpha up-regulates Gi alpha and G beta proteins and adenylyl cyclase responsiveness in rat cardiomyocytes. 164 97

In the present work we evaluated the interactions of adrenergic receptors with phospholipase-C (PLC) and protein kinase-C (PKC), using an in vitro system of hypothalamic neurons and astroglial cells in primary cultures. The study was performed on immature neurons after 7 days in vitro (7 Div), that is before synaptogenesis, as well as on mature cells (14 Div). Comparisons were made between neurons and glial cells at the corresponding developmental stages. Norepinephrine (NE) increased inositol phosphates (IPs) formation in a dose- and time-dependent manner. The NE effect was mediated by alpha 1-receptor (alpha 1R) and was observed in young cells before synaptogenesis as well as in mature neuronal cultures; its amplitude was enhanced during the latter stage of the neuronal development. The coupling of alpha 1R with PLC was partially sensitive to pertussis toxin treatment and did not implicate the activation of calcium voltage-dependent channels. Activation of PKC by 12-O-Tetradecanoylphorbol 13-acetate (TPA) inhibited in a time-dependent manner the NE-stimulated production of IPs in young and mature hypothalamic neurons; however, in PKC depleted cells NE-induced IPs formation remained unchanged. In hypothalamic astroglial cell cultures the adrenergic stimulus of IPs generation was also mediated by alpha 1R. The effect was observed at both developmental stages, with a greater response in 14 Div cultures, and was insensitive to pertussis toxin treatment. As in neurons, activation of PKC resulted in inhibition of NE-induced IPs formation. These data indicate that functional interrelation between alpha 1R, PLC, and PKC is already present in immature neurons and glial cells and progressively develops in culture.
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PMID:Alpha 1-adrenergic receptor coupling with phospholipase-C is negatively regulated by protein kinase-C in primary cultures of hypothalamic neurons and glial cells. 165 54

Noradrenaline inhibits in rat islets the stimulation of insulin secretion induced by glucose and its potentiation by palmitate, but the signalling system responsible remains unknown. We have tested the hypothesis that noradrenaline-induced inhibition is mediated by an elevation of cyclic GMP (cGMP) levels. The analogue 8-Br-cGMP decreases dose-dependently the potentiation by palmitate of glucose-induced insulin secretion, whereas it only slightly affects the proper effect of glucose. Similarly, it abolishes palmitate acceleration of glucose-induced 45Ca2+ uptake without modifying the sugar effect. Finally, 8-Br-cGMP completely inhibits the stimulation of the lipid synthesis de novo induced by palmitate, but not that caused by glucose alone. On the other hand, noradrenaline increases dose-dependently islet cGMP content, with alpha 2-adrenergic specificity. As noradrenaline-induced elevation of cGMP is sensitive to pertussis toxin, it probably results from alpha 2-adrenoceptor activation of islet guanylate cyclase through a guanine nucleotide regulatory protein. It is concluded that the elevated cGMP levels mediate noradrenaline inhibition of lipid synthesis de novo, and hence of acceleration by palmitate of 45Ca2+ uptake and insulin secretion in the presence of glucose.
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PMID:Does cyclic guanosine monophosphate mediate noradrenaline-induced inhibition of islet insulin secretion stimulated by glucose and palmitate? 165 40


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