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 calcium current (ICa) was recorded in guinea-pig ventricular myocytes superfused with Na+,K(+)-free solution and dialysed with a substrate-free solution (minimum intracellular solution, MICS). A dual tight-seal pipette method was often used to permit pressure-enhanced dialysis of a test solution after a given pre-dialysis. 2. In dual-pipette experiments, test dialysates contained 100 mM-GTP-gamma-S (guanosine 5'-O-(3-thiotriphosphate] or 100 microM-GMP-PNP (guanyl-5'-imidodiphosphate). These non-hydrolysable analogues of guanosine triphosphate (GTP) enhanced ICa amplitude (+ 10 mV) by 20-40%. Dialysates containing 100 microM-GTP or GDP-beta-S (guanosine 5'-O-(2-thiodiphosphate] were ineffective, and pre-dialysis with GDP-beta-S blocked stimulation by GTP-gamma-S. 3. Non-hydrolysable GTP analogues slowed the inactivation of ICa and shifted the voltage eliciting maximum ICa by 5-10 mV in the negative direction. 4. ICa enhancement by GTP analogues was attributed to the activation of three GTP-binding regulatory (G) proteins (Gi, Gp and Gs). In single-pipette experiments, the inactivation of Gi by pre-treatment with pertussis toxin did not block enhancement, and a Gp-activating regimen (external acetylcholine-internal GTP) was without effect. Thus, it is probable that the effects of GTP analogues on ICa were primarily mediated by Gs activation. 5. PI-MICS dialysates contained phosphorylation-pathway inhibitors and were used to inhibit Ca2+ channel phosphorylation via the adenyl cyclase pathway. These were deemed effective since forskolin (1-5 microM) doubled ICa during control dialysis but was without effect after 8 min PI-MICS dialysis. However, 0.1 microM-isoprenaline increased ICa by 35% in myocytes totally unresponsive to forskolin, suggesting that beta-adrenergic receptor occupation can stimulate ICa even when the phosphorylation pathway is blocked. 6. After prolonged dialysis of myocytes with PI-MICS, ICa was still enhanced by pressure-assisted dialysis of 100 microM-GTP-gamma-S or GMP-PNP. We conclude that activated Gs has a direct effect on cardiac Ca2+ channels.
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PMID:Whole-cell calcium current in guinea-pig ventricular myocytes dialysed with guanine nucleotides. 216 69

The mechanism of muscarinic inhibition of the Ca-current (ICa) was studied in ventricular myocytes of guinea pig hearts and the following results were obtained. Acetylcholine (ACh) in concentrations up to 10(-4) M had little effect, if any, on ICa in control cells. ACh reduced the isoprenaline (ISP)-induced increase of ICa. The dose-response-relation (ISP concentration vs. ICa density) was shifted by ACh towards higher ISP concentrations. But both, at low and high ISP concentrations ACh had nor or little effect. ACh was ineffective when ICa was increased by dialysing the cell with catalytic subunit of cAMP-dependent protein kinase or cAMP. ACh reduced ICa enhanced by isobutylmethylxanthine or by forskolin. ACh did not depress ICa when the cell was dialysed with the non-hydrolysable GTP-derivative, GMP-PNP. In this condition the beta-adrenergic enhancement of ICa was also absent. Pertussis toxin, which is known to inhibit the inhibitory transducer protein (Ni), abolished the ACh response. We concluded from these results that ACh depresses ICa by inhibiting, via Ni, the cAMP production.
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PMID:On the mechanism of muscarinic inhibition of the cardiac Ca current. 242 6

The intracellular mechanisms by which cardiac Ca current (ICa) and the delayed outward K current (IK) are modulated during beta-adrenergic or muscarinic stimulation were investigated at the level of both single-channel and whole-cell currents in single ventricular myocytes of guinea-pigs. Superfusion of cells with beta-adrenergic agonist increased the amplitude of whole-cell ICa in a dose-dependent manner. In the single-channel recording, neither the amplitude of elementary current nor the total number of active channels was affected but the number of blank records was markedly reduced resulting in a larger amplitude of the ensemble average current. Intracellular dialysis of cells with cyclic AMP (cAMP) or the catalytic (C) subunit of cAMP-dependent protein kinase (cAMP-PK) produced a dose-dependent increase in the amplitude of ICa and IK. A non-hydrolysable ATP analogue, AMP-PNP, reduced whereas ATP gamma S enhanced the effects of beta-agonist on ICa and IK, suggesting an involvement of protein phosphorylation during the enhancement of these currents. The regulatory subunit of cAMP-PK, the heat-stable protein-kinase inhibitor (PKI) and type-1 protein phosphatase antagonized the beta-adrenergic enhancement of ICa and IK, but did not eliminate ICa. Acetylcholine (ACh) reduced the amplitude of ICa when ICa was enhanced by either beta-adrenergic agonist, forskolin or 3-isobutyl-1-methyl-xanthine but did ACh not when ICa was enhanced by intracellular dialysis with cAMP or C subunit, suggesting that muscarinic inhibition occurs at the level of adenylate cyclase. Non-hydrolysable GTP analogue, GMP-PNP, uncoupled both beta-adrenergic and muscarinic modulation of ICa. Pertussis toxin selectively eliminated the effect of ACh on ICa. Based on these results, we concluded that the activities of the Ca channel and the delayed outward K channel are controlled by the action of neurotransmitters, which are mediated by GTP-binding proteins and cAMP-dependent protein phosphorylation. It is suggested that phosphorylation of 'Ca-channel-related protein' leads to an increased open probability without changing the total number of channels or the elementary current amplitude.
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PMID:Intracellular control of calcium and potassium currents in cardiac cells. 243 80

Electrophysiological data support the existence of GTP-binding proteins interacting with voltage dependent calcium channels. Along this line the present study investigates the effect of GMP-PNP, a stable GTP analogue, on the displacement of [3H]-PN 200-110 binding by agonist and antagonist dihydropyridines in synaptic membranes prepared from rat cortex. The results show that GMP-PNP increases the ability of the agonist dihydropyridine BAY K 8644 to displace [3H]-PN 200-110 binding. The in vivo treatment with Pertussis Toxin abolishes the effect produced by the non-hydrolysable GTP analogue.
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PMID:Direct coupling of a G-protein to dihydropyridine binding sites. 246 Nov 98

Electropermeabilized human neutrophils were used to investigate the possible role of G-proteins in the respiratory burst elicited by concanavalin A (Con A). The Con A-induced activation of the NADPH oxidase was not inhibited by either pertussis toxin or cholera toxin. However, the burst was inhibited by GDP and GDP beta S providing evidence for the involvement of a G-protein(s). O2 consumption in Con A-stimulated cells was dependent on both ATP and Mg2+. ATP could be substituted by ATP gamma S but not by the non-hydrolyzable analog AMP-PNP, suggesting involvement of phosphotransferase reactions. It is concluded that at least two distinct types of G-proteins are capable of inducing the respiratory burst in neutrophils and that accumulation of phosphorylated intermediates may be essential for activation of the respiratory burst by the lectin.
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PMID:Concanavalin A stimulation of O2 consumption in electropermeabilized neutrophils via a pertussis toxin-insensitive G protein. 250 97

1. Voltage-activated Ca2+ channel currents were recorded from cultured rat dorsal root ganglion (DRG) neurones using the whole-cell clamp technique with Ba2+ as the charge carrier. 2. Inclusion of the GTP analogue guanosine 5'-O-3-thiotriphosphate (GTP-gamma-S, 500 microM) or guanylylimidodiphosphate (GMP-PNP, 500 microM) or GTP itself (1 mM) in the patch pipette solution resulted in a smaller, slowly activating Ca2+ channel current which did not inactivate during a 100 ms voltage step. This current was inhibited by CdCl2 (10-100 microM) and omega-conotoxin (1 microM). 3. Nifedipine (5 microM), (-)-(R)-201-791 (5 microM), D600 (10 microM), and diltiazem (30 microM) inhibited Ca2+ channel currents recorded from control neurones, although in some cells a biphasic response was observed, with an initial increase preceding the inhibition of the currents. In the presence of internal GTP-gamma-S, at a holding potential (VH) of -80 mV, only potentiation of the Ca2+ channel current was observed in the presence of all three Ca2+ channel ligands. Internal GMP-PNP, while less effective than GTP-gamma-S, also resulted in D600 showing an agonist response. Similarly, in the presence of internal GTP (1 mM), (-)-(R)-202-791 gave a prolonged agonist response. 4. Nifedipine, whether acting as an antagonist in control cells or as an agonist in GTP-gamma-S-containing cells, induced a shift to more hyperpolarized potentials of the steady-state inactivation curves. 5. Potentiation of Ca2+ channel currents induced by D600 in GTP-gamma-S-containing cells, was not observed when the neurones were pre-treated with pertussis toxin. The presence of internal GDP-beta-S (500 microM) did not significantly alter the maximum inhibitory action of D600 compared with controls. However, 1 mM-GDP-beta-S increased the rate of onset of inhibition by (-)-(R)-202-791. 6. Depolarizing VH to -30 mV accelerated the onset of inhibition induced by the Ca2+ channel ligands in control cells. In the presence of internal GTP-gamma-S at VH -30 mV, biphasic responses were produced by all the Ca2+ channel antagonist ligands with initial stimulation for 1-2 min being followed by inhibition of the Ca2+ channel currents. 7. The agonist actions of (+)-(S)-202-791 were potentiated by the presence of internal GTP-gamma-S. 8. The expression of an agonist response to (-)-(R)-202-791 induced by internal GTP-gamma-S was also present in sympathetic neurones cultured from adult rat superior cervical ganglion (SCG).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interaction between calcium channel ligands and guanine nucleotides in cultured rat sensory and sympathetic neurones. 255 37

Isolated human polymorphonuclear (PMN) leukocyte plasma membranes express high affinity (mean Kd = 0.12 nM) and low affinity (mean Kd = 50 nM) receptors for the chemotactic factor leukotriene B4 (5(S),12(R)-dihydroxy-eicosa-6,14 cis-8,10 trans-tetraenoic acid; LTB4) that are similar to those on intact PMN leukocytes. A portion of high affinity LTB4-R on PMN leukocyte membranes were converted to the low affinity state by GTP (mean +/- SE = 28.6 +/- 14.0%) and nonhydrolyzable GTP analogues, such as 5'-guanylylimidodiphosphate (GMP-PNP), in a concentration-dependent, nucleotide-specific, and reversible manner, without altering the intrinsic binding affinities of either class. [3H]GMP-PNP bound specifically to one class of receptors (mean Kd = 13 nM) on PMN leukocyte membranes. The interdependence of the LTB4-binding membrane protein and guanine nucleotide-binding protein was suggested by the capacity of LTB4 to enhance by a maximum of 150% the binding of [3H]GMP-PNP to PMN leukocyte membranes by increasing the number, but not altering the affinity, of receptors for GMP-PNP. Pertussis toxin, but not cholera toxin, reversed the enhancement of binding of [3H]GMP-PNP produced by LTB4. Guanine nucleotide-binding proteins and high affinity LTB4-R thus exhibit a mutual regulation that differs mechanistically from that of peptide chemotactic factor receptors on PMN leukocytes.
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PMID:Selective modulation by guanine nucleotides of the high affinity subset of plasma membrane receptors for leukotriene B4 on human polymorphonuclear leukocytes. 283 4

The nonhydrolyzable GTP analogue guanosine 5'-(beta, gamma-imido)triphosphate (GMP-PNP) produced an ATP-dependent but Ca2+-independent stimulation of [3H]norepinephrine release from permeabilized chromaffin cells. This stimulation of secretion was 25-35% of the secretion induced by 10 microM Ca2+. A similar Ca2+-independent stimulation was produced by other non-hydrolyzable GTP analogues. No effect was seen with a variety of other nucleotides, including GTP. The GMP-PNP effect was specifically inhibited by low concentrations of guanine nucleotides. Addition of cAMP did not mimic the Ca2+-independent GMP-PNP effect, but did slightly enhance Ca2+-dependent secretion. Pretreatment with pertussis toxin had no effect on Ca2+-dependent secretion or on the GMP-PNP effect. There was no detectable diglyceride or inositol phosphate produced during GMP-PNP treatment, and addition of diglyceride and inositol trisphosphate did not induce secretion. Guanosine 5'-(beta-thio)diphosphate (GDP-beta-S), in addition to its ability to inhibit the GMP-PNP effect, partially inhibited Ca2+-dependent secretion. At 10 microM free Ca2+, the effects of GMP-PNP and Ca2+ were nonadditive. In fact, secretion in the presence of both GMP-PNP and 10 microM Ca2+ was slightly less than secretion due to Ca2+ alone. These data suggest that a guanine nucleotide-dependent process interacts in some way with one or more components of the normal Ca2+-dependent secretory pathway. However, it may not be an intrinsic part of the mechanism underlying Ca2+-dependent secretion.
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PMID:Guanine nucleotide effects on catecholamine secretion from digitonin-permeabilized adrenal chromaffin cells. 301 21

The stimulation of gonadotropin release from pituitary cell cultures by GnRH has been linked to inositol phospholipid breakdown to diacylglycerols and subsequent activation of protein kinase C as well as Ca2+ mobilization. In order to examine the means of receptor coupling to a phospholipase C-type reaction, we evaluated the role of guanine nucleotides in inositol phospholipid breakdown. In these studies ATP (50 microM) was used for cell permeabilization to allow guanine nucleotides access to the intracellular compartment. Under these conditions GTP and the GTP analog, guanylylimidodiphosphate (GMP-PNP), stimulated a time- and dose-dependent increase in LH release and inositol phosphate accumulation. These actions of GTP and GMP-PNP were not observed unless ATP was included in the treatment media. Other closely related nucleotides and nucleosides alone, or in the presence of ATP, did not elevate LH release above basal levels. We also evaluated the actions of pertussis toxin and cholera toxin on mediating the effect of GTP, GMP-PNP, and GnRH on LH release and inositol phosphate accumulation. After treatment with these agents, no changes were observed in the ability of GnRH, GTP, or GMP-PNP to stimulate either LH release or inositol phosphate accumulation. The additional observation that GnRH-, GTP-, or GMP-PNP-stimulated LH release and inositol phosphate accumulation were blocked by a potent GnRH antagonist suggests that a G protein is functionally associated with the GnRH receptor recognition site.
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PMID:Stimulation of luteinizing hormone (LH) release and phospholipid breakdown by guanosine triphosphate in permeabilized pituitary gonadotropes: antagonist action suggests association of a G protein and gonadotropin-releasing hormone receptor. 302 16

Neuroblastoma X glioma hybrid cells NG108-15 were treated with a toxin derived from Bordetella pertussis. As compared to control cells grown in the absence of toxin, the inhibitory effects of opioid agonists upon cAMP formation were dose-dependently impaired by a non-competitive mechanism. Radioligand binding studies revealed that opioid agonist binding was dramatically reduced in toxin-treated membranes when tested in the presence of Na+/Mg++/GMP-PNP. Further, the potencies of guanine nucleotides to decrease opioid agonist binding were differentially modulated. These studies may facilitate our understanding of the mechanisms responsible for acute and chronic opiate effects.
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PMID:Pertussis toxin decreases opiate receptor binding and adenylate inhibition in a neuroblastoma x glioma hybrid cell line. 631 65


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