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. (-)Baclofen reduces inhibitory postsynaptic potentials (IPSPs) and the associated synaptic currents (IPSCs) at inhibitory GABAergic synapses between cultured rat hippocampal neurones. The reversal potential for the IPSC is unaltered. 2. The effect of (-)baclofen is concentration dependent; the EC50 for (-)baclofen is approximately 5 microM. 3. Statistical analyses of the amplitude fluctuations of the IPSC in the presence of (-)baclofen suggested a presynaptic location for the depression of synaptic transmission by (-)baclofen. In control experiments, lowering extracellular Ca2+ produced similar effects. (-)Baclofen has no detectable postsynaptic actions in these cultured neurones. 4. Phaclofen (0.2-0.5 mM) increases IPSC amplitude but does not significantly block the depressant effect of (-)baclofen on synaptic transmission. 5. The effect of (-)baclofen is not blocked by pertussis toxin pre-treatment. 6. It is concluded that (-)baclofen acts presynaptically to reduce the release of GABA. The mechanism by which release is reduced may involve a phaclofen-insensitive GABAB receptor.
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PMID:On the presynaptic action of baclofen at inhibitory synapses between cultured rat hippocampal neurones. 235 87

In primary cultures of cerebellar granule cells, the gamma aminobutyric acid B (GABAB) receptor couples to an inhibitory mechanism of adenylate cyclase. The inhibition of adenylate cyclase can be observed either by the measurement of cellular cyclic AMP content or by in vitro measurement of adenylate cyclase from plasma membrane of these cerebellar granule cells. The GABAB receptors can be stimulated by GABA and the GABA analog, baclofen. This receptor-mediated inhibition of adenylate cyclase was blocked by the pertussis toxin, islet-activating protein. Furthermore, the authors show that islet-activating protein catalyzed the ADP ribosylation of the guanine nucleotide inhibitory unit (MW 41,000) in the cerebellar granule cells. In summary, the authors provide evidence supporting the presence of a GABAB receptor in the cerebellar granule cells and suggest that this receptor couples with the guanine nucleotide inhibitory unit to inhibit the formation of cyclic AMP.
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PMID:Gamma aminobutyric acid B receptor-mediated inhibition of adenylate cyclase in cultured cerebellar granule cells: blockade by islet-activating protein. 243 96

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

Regulation of neuronal calcium channels by GTP-binding proteins (G proteins) is likely to be an important mechanism by which inhibitory transmitters influence excitation-secretion coupling in presynaptic nerve endings. Here, we report that in peripheral sensory neurons from embryonic chick dorsal root ganglia (DRG), the G protein-mediated inhibition of voltage-dependent calcium channels may best explain how norepinephrine (NE) and GABA inhibit the electrically evoked, calcium-dependent release of substance P (SP). As is the case for the previously reported inhibitory actions of these transmitters on DRG cell calcium channels, we demonstrate that NE and GABA inhibit peptide secretion through activation of alpha-adrenergic and GABAb receptors that are functionally coupled to pertussis toxin (PTX)-sensitive G proteins. Pretreatment of DRG cell cultures with PTX blocked the ability of NE and GABA to inhibit the release of SP, an action correlated with PTX-catalyzed ADP-ribosylation of membrane proteins with apparent molecular weight (Mr) of 40-41 kDa. Western immunoblot analysis of chick DRG cell membrane proteins using antisera directed against synthetic peptides corresponding to amino acid sequences predicted from cDNAs for PTX-sensitive G protein alpha subunits revealed a minimum of 2 Gi-like proteins (Mr 40 and 41 kDa) and a third Go-like protein (Mr 40 kD). Significantly, these findings implicate Gi- and/or Go-like GTP-binding proteins as mediators of presynaptic inhibition in peripheral sensory neurons.
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PMID:G proteins couple alpha-adrenergic and GABAb receptors to inhibition of peptide secretion from peripheral sensory neurons. 246 94

The GABA application evoked fast picrotoxin-sensitive depolarization as well as slow depolarization with decreasing membrane conductivity and hyperpolarization with increasing membrane conductivity in the neurons of the rat dorsal root ganglion. The slow picrotoxin-resistant responses to GABA were initiated with phenibut. The phenibut effects were modulated by cAMP concentration and inhibited by the pertussis toxin. The reversal potential of the phenibut effects was equal to the potassium equilibrium one. The phenibut effects were reduced by increasing K+ and Ca+ extracellular concentration, and enhanced in presence of trifluoroperazine.
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PMID:[Analysis of the nature of responses of neurons of rat spinal ganglia evoked by the activation of GABA-B receptors]. 254 67

The technique of radiotracer 36Cl- influx in primary culture of rat cerebellar granule cells was applied to study the mechanism of inactivation of the GABAA receptor-activated chloride channel. During sustained application of GABA, muscimol and THIP the specific bicuculline-sensitive 36Cl- influx tends to decline with time. The sequence in decay half-time is GABA less than muscimol less than THIP. Diazepam accelerates the rate of decay of the peak response to GABA. (-)-Baclofen enhances the rate of decline of the response to muscimol in a dose-dependent manner. Treatment of the cells with pertussis toxin antagonized the effect of (-)-baclofen. It is concluded that rat neonatal cerebellar neurons maintained in tissue culture exhibit complex inactivation of the GABAA channel, indicating some interaction with the GABAB receptor system.
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PMID:36Cl- flux measurements on GABAA receptor-activated chloride exchange. Multiple mechanisms of the chloride channel inactivation. 254 12

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

Neuronal firing during experimental convulsions triggered a large increase in brain eicosanoid synthesis. Mature astrocytes are an important source of cerebral prostanoids. Endogenously formed prostaglandins possess anticonvulsive properties of biological relevance. These conclusions suggest new ideas that might explain the formation and functions of prostanoids in the brain. First, as augmented neuronal discharge is a prerequisite for enhanced prostanoid synthesis during seizures, a functional coupling between firing neurons and prostanoid-forming astrocytes may be expected. Second, the anticonvulsive effects of endogenous prostanoids suggest that astroglia-derived substances might regulate neuronal activity. The phenomenon of convulsion-induced prostanoid synthesis may, therefore, represent a new example of neuron-glia interaction. Neither K+-induced membrane depolarization nor receptor activation by drugs with affinity to alpha or beta adrenoceptors, dopamine, serotonin, muscarine, histamine, GABA, glutamate, aspartate, adenosine, and opioid receptors evoked eicosanoid synthesis in astrocytes. The only physiologically relevant ligand that induced prostanoid synthesis concentration dependently in astrocytes was ATP and related nucleotide triphosphates, as well as nucleotide disphosphates. In peripheral nerves ATP serves as a cotransmitter. The effect of the P2 agonists was reduced by pertussis toxin. The mechanism by which eicosanoids regulate neuronal activity remains to be elucidated.
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PMID:Formation and function of eicosanoids in the central nervous system. 267 46

We have investigated the action of pertussis toxin on a range of receptor-mediated responses of the rat superior cervical ganglion in vitro. The ganglia were treated with pertussis toxin for 24 h at 37 degrees C using an in vitro method. Appropriate controls were also carried out. Pertussis toxin (1 microgram/ml) reduced ganglionic hyperpolarisations mediated by adenosine, alpha 2, 5-HT1A, M2 and GABAB receptors. The GABAB-mediated hyperpolarisation of this preparation, evoked by baclofen and GABA in a bicuculline-resistant manner, has not previously been reported. Pertussis toxin did not reduce ganglionic depolarisations evoked by potassium chloride and 5-HT3, GABAA and nicotinic receptors. Depolarisations to muscarine and noradrenaline, probably mediated by M1 and beta-receptors, also appeared to be resistant to pertussis toxin. The similar sensitivity of the various ganglionic hyperpolarisations to pertussis toxin indicates that they may all be mediated by similar G-proteins.
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PMID:Pertussis toxin sensitivity of drug-induced potentials on the rat superior cervical ganglion. 272 73

The possible involvement of GABA in the control of the rhythmical bursting activity (RBA) of septo-hippocampal neurons (SHNs) has been studied in the rat in vivo. The discharge frequency of SHNs was modified by the iontophoretic application of a GABA agonist and antagonist as well as by the application of the GABA uptake blocker, nipecotic acid. The GABAB agonist baclofen inhibited the SHNs' activity, this effect being antagonized by the GABAB antagonist phaclofen. However, these different pharmacological manipulations did not modify the RBA frequency. Pretreatment of the rats with pertussis toxin, a substance which is known to block the events mediated by G-proteins (Gi or Go), decreased the RBA frequency. Neither agonists nor antagonists of GABAA or GABAB types had significant effects on the rhythmical bursting activity of SHNs. The effect of pertussis toxin suggests that other neurotransmitters or intrinsic mechanisms involving a G-protein influence this rhythm.
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PMID:Rhythmical bursting activity and GABAergic mechanisms in the medial septum of normal and pertussis toxin-pretreated rats. 279 83


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