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)

When gamma-aminobutyric acid (GABA) or baclofen were applied to cultured rat hippocampal neurons, single-channel potassium currents appeared after a delay of 30 s or more in patches of membrane on the cell surface isolated from the agonists by the recording pipette. The appearance of currents in patches not exposed to agonist, the delay in their appearance and the suppression of currents in cells pre-incubated with pertussis toxin indicate the involvement of an intracellular second messenger system. The channels were associated with a GABAB receptor rather than a GABAA receptor as they were blocked by baclofen, a GABAB antagonist, but were not affected by bicuculline, a GABAA antagonist. A feature of the single channel currents was their variable amplitude: they had a maximum conductance of ca. 70 pS and displayed many lower conductance states that were integral multiples of 5-6 pS. In several cells exposed to GABA or baclofen, first small currents and then progressively larger currents appeared: current amplitude was a multiple of an elementary current. It is suggested that binding of GABA to GABAB receptors activates a second messenger system causing opening of oligomeric potassium channels.
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PMID:GABA-induced potassium channels in cultured neurons. 197 42

1. We have examined the effects of L-glutamate and gamma-aminobutyric acid (GABA) on the presynaptic membrane of spiny lobster by the use of intra-axonal recording near the nerve terminals. 2. Application of glutamate to the synaptic region produced hyperpolarization in the presynaptic membrane but depolarization in the postsynaptic membrane. The presynaptic glutamate potential (PGP) is generated by an activation of K+ channels, as evidenced by its dependence on external K+ concentration. 3. The PGP was not affected by a spider toxin (JSTX), which blocks the postsynaptic glutamate receptor. By contrast, pertussis toxin (IAP) effectively blocked the PGP without affecting the resting conductance channels or action potentials in the presynaptic membrane. 4. Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), a hydrolysis-resistant analogue of GTP, blocked the PGP, suggesting the involvement of a G protein in the generation of K+ current. 5. Application of GABA induced depolarization or hyperpolarization in the presynaptic axon depending on the resting membrane potential. By reducing external Cl-, GABA-induced hyperpolarizations were converted to depolarizations, indicating that they are mainly mediated by Cl-. 6. In contrast to GABA, baclofen consistently induced hyperpolarization in low Cl- solution as well as in normal solution. Baclofen-induced hyperpolarization was blocked by IAP, indicating the mediation of G protein. 7. These results suggest that the presynaptic membrane of lobster neuromuscular synapse has entirely different types of amino-acid receptors from those in the postsynaptic membrane. Both the excitatory and the inhibitory axonal membrane have glutamate ("glutamateB") and GABAB receptors, which activate K+ channels via G protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:G protein is coupled to presynaptic glutamate and GABA receptors in lobster neuromuscular synapse. 215 71

The effects, on membrane potential, of dopamine (DA) and gamma-aminobutyric acid (GABA), transmitters present in the secreto-inhibitor innervation to the melanotrophs, were monitored in primary cultures of rat melanotrophs with bis-oxonol. DA and GABA, acting through D2 and GABAB receptors, hyperpolarized the melanotrophs. Hyperpolarization was not suppressed by tetrodotoxin but was prevented by pertussis toxin and may thus be due to a G protein mediated mechanism. Pertussis toxin also blocked the effects mediated by the two receptors to reduce intracellular free Ca2+ ([Ca2+]i).
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PMID:Dopamine (D2) or gamma-aminobutyric acid (GABAB) receptor activation hyperpolarizes rat melanotrophs and pertussis toxin blocks these responses and the accompanying fall in [Ca2+]i. 216 38

The modulation of voltage-dependent calcium channels by hormones and neurotransmitters has important implications for the control of many Ca2+-dependent cellular functions including exocytosis and contractility. We made use of electrophysiological techniques, including whole-cell patch-clamp recordings from dorsal root ganglion (DRG) neurones, to demonstrate a role for GTP-binding proteins (G-proteins) as signal transducers in the noradrenaline- and gamma-aminobutyric acid (GABA)-induced inhibition of voltage-dependent calcium channels. This action of the transmitters was blocked by: (1) preincubation of the cells with pertussis toxin (a bacterial exotoxin catalysing ADP-ribosylation of G-proteins); or (2) intracellular administration of guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S), a non-hydrolysable analogue of GDP that competitively inhibits the binding of GTP to G-proteins. Our findings provide the first direct demonstration of the G-protein-mediated inhibition of voltage-dependent calcium channels by neurotransmitters. This mode of transmitter action may explain the ability of noradrenaline and GABA to presynaptically inhibit Ca2+-dependent neurosecretion from DRG sensory neurones.
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PMID:GTP-binding proteins mediate transmitter inhibition of voltage-dependent calcium channels. 241 57

In neuronal cells, opioid peptides and opiates inhibit neurotransmitter release, which is a calcium-dependent process. They also inhibit adenylyl cyclase, presumably via the membrane signal-transducing component, Gi, a guanine nucleotide-binding protein (G-protein). No causal relationship between these two events has yet been demonstrated. Besides Gi, membranes of neuronal tissues contain large amounts of Go, a G-protein with unknown function. Both G-proteins are heterotrimers consisting of alpha-, beta- and gamma-subunits; the alpha-subunits can be ADP-ribosylated by an exotoxin from Bordetella pertussis (PT), which modification inhibits receptor-mediated activation of the G-protein. It was recently shown that noradrenaline, dopamine and gamma-aminobutyric acid (GABA) inhibit the voltage-dependent calcium channels in dorsal root and sympathetic ganglia; this inhibition is mimicked by intracellular application of guanine nucleotides and blocked by PT, suggesting the involvement of a G-protein. Here we report an inhibitory effect of the opioid D-Ala2, D-Leu5-enkephalin (DADLE) on the calcium current (ICa) in neuroblastoma X glioma hybrid cells (N X G cells). Pretreatment with PT almost completely abolishes the DADLE effect. The effect is restored by intracellular application of Gi and Go. As the alpha-subunit of Go (with or without beta-gamma complex) is 10 times more potent than Gi, we propose that Go is involved in the functional coupling of opiate receptors to neuronal voltage-dependent calcium channels.
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PMID:The GTP-binding protein, Go, regulates neuronal calcium channels. 243 90

1. The effect of intracellular application of the hydrolysis-resistant GTP and GDP analogues, guanosine 5'-O-3-thiotriphosphate (GTP-gamma-S), and guanosine 5'-O-2-thiodiphosphate (GDP-beta-S) has been examined on voltage-activated calcium-channel currents and the ability of the gamma-aminobutyric acid B agonist baclofen to inhibit them, in cultured rat dorsal root ganglion (d.r.g.) neurones. 2. Under control conditions, the calcium-channel current, recorded using the whole-cell patch technique with Ba2+ rather than Ca2+ as the permeant divalent cation, consists of an inactivating and a sustained current. In the presence of 500 microM-GTP-gamma-S included in the patch pipette, the calcium-channel current was activated more slowly and was largely non-inactivating during the 100 ms depolarization voltage step. The effects of GTP-gamma-S were abolished by pre-treatment of cells with pertussis toxin. 3. The calcium-channel current recorded in the presence of 500 microM-GDP-beta-S had a more marked transient component than the control calcium-channel current. The proportion of transient calcium-channel current in the presence of GDP-beta-S was not reduced in Na+-free medium. 4. No statistically significant effects of GTP-gamma-S and GDP-beta-S were observed on the calcium-activated potassium current IK(Ca), the transient outward potassium current activated in Ca2+-free medium, or on the inwardly rectifying current (Ih) activated by hyperpolarization. 5. GTP-gamma-S increased the ability of baclofen to inhibit calcium-channel currents, whereas this was decreased by GDP-beta-S and by pre-treatment of cells with pertussis toxin. The half-maximal effective dose (EC50) for baclofen was 2 microM in the presence of GTP-gamma-S, 15 microM for control and 50 microM in the presence of GDP-beta-S. Comparable results were obtained using a single concentration of the adenosine agonist 2-chloroadenosine (2-CA, 0.05 microM) to inhibit calcium-channel currents; its effect was significantly increased by GTP-gamma-S and reduced by GDP-beta-S. 6. The ability of baclofen to inhibit calcium-channel currents was not affected by 1 microM-forskolin or 50 microM-intracellular cyclic AMP. 7. It is concluded that calcium channels in d.r.g.s are associated with a nucleotide binding protein, and that this mediates the effect of baclofen and 2-CA on calcium-channel currents. The ability of GTP-gamma-S to inhibit the transient component of calcium-channel currents in the absence of agonist may represent a means of differentially regulating calcium-channel activity.
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PMID:Calcium channel currents and their inhibition by (-)-baclofen in rat sensory neurones: modulation by guanine nucleotides. 244 60

1. Intracellular recordings were made from 193 substantia nigra zona compacta neurones in slices of rat mesencephalon. All cells were hyperpolarized by baclofen; this was accompanied by a fall in input resistance. Cells voltage clamped at -60 mV showed an outward current associated with a conductance increase in response to baclofen. The baclofen effects were concentration dependent (effective range 0.3-30 microM); the concentration producing half the maximal effect was 1.5 microM. (-)-Baclofen was 300-700 times more potent than (+)-baclofen. 2. The potential change or membrane current caused by baclofen reversed polarity at -108.8 +/- 1.1 mV (n = 10) when the potassium ion concentration was 2.5 mM, -96.0 +/- 2.8 mV (n = 3) in 4.5 mM-potassium and -76.6 +/- 1.7 mV (n = 5) in 10.5 mM-potassium. The relationship between reversal potential and potassium concentration conformed to the Nernst equation. 3. Dopamine was also applied to 119 of these neurones; all exhibited either a hyperpolarization or an outward current. 4. Baclofen and dopamine outward currents were reduced reversibly by barium (100-300 microM) and tetraethylammonium (10 mM). Superfusion for 5-10 min with solutions presumed to block calcium currents reduced, but did not abolish, responses to baclofen. The effect of baclofen persisted in tetrodotoxin (1 microM). 5. Superfusion of gamma-aminobutyric acid (GABA, 0.3-3 mM) caused either membrane depolarization or hyperpolarization, accompanied by a fall in input resistance. The depolarization was mimicked by muscimol (10 microM) and blocked by bicuculline methiodide (10-100 microM); the hyperpolarization was resistant to bicuculline. Nipecotic acid (500 microM) enhanced the effect of GABA, but was without effect upon the actions of muscimol and baclofen. 6. The effect of dopamine was enhanced by cocaine (10 microM) and antagonized by (-)-sulpiride (0.1-1 microM), whereas the actions of baclofen were unaffected by cocaine or (-)-sulpiride. The maximum outward current produced by dopamine was approximately half that produced by baclofen. 7. Outward currents produced by dopamine were reversibly occluded by maximal outward currents caused by baclofen. 8. Baclofen and dopamine hyperpolarizations were unaffected by intracerebroventricular injection of animals with pertussis toxin. 9. Cells impaled with electrodes containing guanosine 5'-O-(3-thiotriphosphate) (1 mM) were hyperpolarized by both baclofen and dopamine, but the membrane potential did not fully return to its original level when agonist application was discontinued. 10. It is concluded that activation of both dopamine D2 and GABAB receptors may increase the same potassium conductance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:On the potassium conductance increase activated by GABAB and dopamine D2 receptors in rat substantia nigra neurones. 245 76

1. The physiological and pharmacological properties of identified septo-hippocampal neurones (SHNs) have been studied in rats pretreated with the bacterial toxin, pertussis toxin (PTX). 2. In rats anaesthetized with urethane and pretreated with PTX, the axonal conduction velocity was unchanged while the mean spontaneous activity was significantly increased. 3. PTX pretreatment had no effect on responses of SHNs to the iontophoretic application of gamma-aminobutyric acid (GABA) and cholinoceptor agonists (acetylcholine or carbachol). 4. Baclofen and 5-hydroxytryptamine (5-HT), almost exclusively inhibitory in control rats, had little effect or an excitatory effect in PTX pretreated rats. 5. These results suggest the involvement of a pertussis toxin-sensitive G-protein in responses medicated by 5-HT and GABAB-receptors but not in responses mediated by cholinoceptors and GABAA-receptors in medial septum neurones projecting into the hippocampus.
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PMID:Involvement of a pertussis toxin-sensitive G-protein in the pharmacological properties of septo-hippocampal neurones. 250 Sep 97

In order to examine the involvement of G-proteins in mediating the different effects of adenosine A1-receptor stimulation in rat hippocampus we injected pertussis toxin (PTX) intraventricularly close to the hippocampus and examined its effect in slices 48-60 h later. The in vivo PTX treatment caused a partial (50 +/- 5%) inhibition of the [32P]ADP ribosylation produced by PTX added together with [32P]NAD in vitro. Such PTX treatment eliminated the electrophysiologically determined gamma-amino-n-butyric acid (GABA)B receptor response in the hippocampal CA1 region, but GABAA effects were unaffected. The adenosine (50 microM)-mediated hyperpolarization and decrease in input resistance as well as the adenosine-mediated inhibition of low calcium-induced bursting in pyramidal CA1 neurons were virtually abolished. The same was true for the decrease in [3H]cyclic AMP accumulation that is produced by the adenosine analogue R-N6-phenylisopropyl adenosine (R-PIA) in forskolin-treated hippocampal slices. As far as modulation of transmitter release was concerned, the R-PIA (1 microM)-induced inhibition of release of both [3H]noradrenaline (NA) and [3H]acetylcholine (ACh) evoked by field stimulation in hippocampal slices was affected hardly or not at all by pertussis toxin treatment. The inhibitory effect of adenosine on field excitatory postsynaptic potential (EPSP)s evoked in the CA1 region was unaltered by PTX pretreatment. The present results show that in vivo pertussis toxin treatment can inhibit some but not all A1-adenosine-receptor effects. This strongly suggests that closely similar A1 receptors might be coupled to G-proteins that differ in their sensitivity to PTX treatment.
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PMID:In vivo pertussis toxin treatment attenuates some, but not all, adenosine A1 effects in slices of the rat hippocampus. 255 Feb 63

The effects of agents known to affect G-proteins on voltage-dependent, tetrodotoxin-sensitive Na+ channels were studied in Xenopus oocytes injected with rat brain RNA, using two-electrode voltage-clamp technique. The non-hydrolysable analogue of GTP, GTP-gamma-S, known to activate G-proteins, inhibited the Na+ current (INa). The decrease in the amplitude of INa was not accompanied by changes in activation or inactivation characteristics of the channel. The non-hydrolysable analogue of GDP, GDP-beta-S, had no effect on INa. The responses to gamma-aminobutyric acid and kainate in the same oocytes were also attenuated by GTP-gamma-S. Pertussis toxin, which inactivates some G-proteins by catalyzing their ADP-ribosylation, enhanced INa, but did not prevent the inhibition of INa by GTP-gamma-S. We conclude that the Na+ channel, and possibly the GABA and kainate receptors and/or channels, are coupled to a G-protein. The activation of the G-protein modulates the channels either directly, or via activation of biochemical cascade possibly involving production of second messengers and channel phosphorylation.
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PMID:Modulation of the voltage-dependent sodium channel by agents affecting G-proteins: a study in Xenopus oocytes injected with brain RNA. 255 1


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