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)

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

To examine the role of guanine nucleotide binding (G) proteins in receptor-mediated inhibition of serotonin (5-HT) neurons, we intracerebrally injected pertussis toxin (0.5-1.0 microgram) into rat midbrain in a region immediately rostral to the dorsal raphe nucleus. The baseline firing rate of extracellularly recorded 5-HT neurons was not significantly affected by pertussis toxin treatment. However, in comparison to saline-injected controls, pertussis toxin-injected animals showed markedly blunted sensitivity to agonists that act at 5-HT autoreceptors (isapirone, 5-HT and LSD) and to baclofen, a GABAB agonist. This pertussis toxin-induced blunting of sensitivity was demonstrated in vivo (with intravenous and iontophoretic application of drugs) and in vitro in the dorsal raphe brain slice preparation. The sensitivity of iontophoretically applied GABA itself was not significantly decreased with pertussis toxin treatment, consistent with evidence that GABA administered in this manner acts on dorsal raphe cells mainly through GABAA receptors. Our data provide strong evidence for the role of a pertussis toxin substrate(s) (presumably a G protein(s] in mediating the inhibition induced by the autoreceptor and GABAB receptor on 5-HT neurons in rat dorsal raphe nucleus.
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PMID:Pertussis toxin blocks 5-HT1A and GABAB receptor-mediated inhibition of serotonergic neurons. 282 89

Pharmacological properties of pre- and postsynaptic GABAB receptors were compared in CA1 hippocampal pyramidal neurons in vitro. The postsynaptic effects mediated by GABAB receptors, i.e., the baclofen-induced hyperpolarization, the bicuculline-resistant GABA response, and the slow inhibitory postsynaptic potential elicited by CA1 afferent stimulation, are all blocked by pertussis toxin (which inactivates some G proteins). These events are also suppressed by stimulating protein kinase C by phorbol esters and blocked by the selective GABAB antagonist phaclofen. In contrast, the baclofen-induced presynaptic depression of the excitatory postsynaptic potential elicited by CA1 afferent stimulation is resistant to the action of pertussis toxin and is not antagonized by phaclofen. However, this presynaptic inhibition can be antagonized by phorbol esters. These results indicate that the pre- and postsynaptic effects mediated by GABAB receptors in hippocampus have distinctly different pharmacological properties and possibly a different coupling mechanism.
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PMID:Pre- and postsynaptic GABAB receptors in the hippocampus have different pharmacological properties. 285 99

Intracellular recordings were made from neurons in rat dorsal raphe in the slice preparation maintained at 37 degrees C. The single-electrode voltage-clamp method was used to measure membrane currents at potentials more negative than rest (-60 mV). Three types of inward rectification were observed: 2 in the absence of any drugs and the third induced by 5-HT 1 and GABA-B receptor agonists. In the absence of any drugs, an inward current activated over 1-2 sec when the membrane potential was stepped to potentials more negative than -70 mV. This current was blocked by cesium (2 mM) and resembles IQ or IH. A second inward current (IIR) occurred at membrane potentials near the potassium equilibrium potential (EK). This inward current activated within the settling time of the clamp and was abolished by both barium (10-100 microM) and cesium (2 mM). 5-HT 1 agonists activated a potassium conductance that hyperpolarized the cells at rest. This potassium conductance was about 2 nS at -60 mV and increased linearly with membrane hyperpolarization to about 4 nS at -120 mV. Baclofen activated a potassium conductance identical in amplitude and voltage dependence to that induced by 5-HT 1 agonists. Both the baclofen- and 5-HT-induced currents were nearly abolished in animals pretreated with pertussis toxin. The results indicate that a common potassium conductance is increased by 5-HT acting on 5-HT 1 receptors and baclofen acting on GABA-B receptors. This potassium conductance rectifies inwardly and is distinct from the Q-current. The ligand-activated potassium conductance also differs from the other form of inward rectification (IIR) in its voltage dependence and sensitivity to pertussis toxin.
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PMID:Voltage- and ligand-activated inwardly rectifying currents in dorsal raphe neurons in vitro. 317 86

In this study, the regulation of striatal cyclic-3',5'-adenosine monophosphate (cAMP) formation and GABA release by dopamine D1 and metabotropic glutamate receptors (mGluR) was studied in brain slices. In the absence of adenosine A2 receptor blockade, the mGluR agonist, 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD) stimulated cAMP accumulation through a pertussis toxin-insensitive mechanism that could be blocked by L-serine-o-phosphate, but not by L(+)-2-amino-3-phosphonopropionic acid. However, in the presence of the adenosine antagonist, 3-isobutyl-1-methylxanthine, 1S,3R-ACPD had no significant effect on basal cAMP, but it inhibited cAMP formation stimulated by the D1 agonist, SKF 38393. This inhibitory response was prevented by pertussis toxin pretreatment and mimicked by L(+)-2-amino-3-phosphonopropionic acid, but it was unaffected by L-serine-o-phosphate. Thus, 1S,3R-ACPD was determined to activate distinct mGluRs in the striatum that mediate either inhibition or activation of cAMP accumulation, with the latter effect being dependent on the activation of adenosine A2 receptors. A potential physiological role for the interaction between the D1 and adenosine-dependent stimulatory metabotropic receptor was sought by examining this interaction on striatal GABA release. SKF 38393 and 1S,3R-ACPD together were found to potentiate striatal GABA release induced by 15 mM K+. The potentiation was blocked by the D1 antagonist, SCH 23390. However, this effect was only partially mimicked by a high concentration of forskolin (100 microM) and was not blocked by L-serine-o-phosphate, thereby suggesting that the stimulatory mGluR does not mediate this potentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of striatal cyclic-3',5'-adenosine monophosphate accumulation and GABA release by glutamate metabotropic and dopamine D1 receptors. 747 79

gamma-Hydroxybutyrate is an endogenous substance of mammalian brain which is primarily derived from GABA. This compound exhibits neuromodulatory influences on dopamine and serotonin synthesis and release in rat brain. These effects are mediated by specific brain receptors which are mainly distributed in the hippocampus, cortex and striatum. In order to characterize this type of receptor, we have studied the possibility that guanosine triphosphate (GTP) and/or pertussis toxin mediated modification of the affinity for gamma-hydroxybutyrate binding to the receptor. Results presented in this paper favor the presence of guanine nucleotide binding proteins (G0 or Gi family), which are coupled to the gamma-hydroxybutyrate receptor, modifying the high-affinity gamma-hydroxybutyrate binding. We conclude that the gamma-hydroxybutyrate receptor in brain belongs to the G-protein family of receptors.
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PMID:gamma-Hydroxybutyrate receptor binding in rat brain is inhibited by guanyl nucleotides and pertussis toxin. 760 25

Three different GABA-insensitive Cl- channels could be resolved in cultured hippocampal neurons using the inside-out patch clamp configuration. The most commonly observed channel revealed an inward rectification with a chord conductance of 40 pS in symmetrical Cl- solutions at a membrane potential of -50 mV and had voltage sensitive gating kinetics. Channel openings were not observed in cell-attached patch, and after excision, several minutes of perfusion of the cytoplasmic side were required before detecting the first openings. The open state probability was increased by guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S 10(-4) M) and reduced by guanosine 5'-O-(2-thiophosphate) (GDP-beta-S 10(-4) M) suggesting its regulation by G proteins. This new identified chloride channel may account for the previously described voltage-sensitive, inward-rectifying whole cell Cl- current which was enhanced by adenosine in a pertussis toxin-sensitive manner.
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PMID:GTP- and GDP-analogues modulate an inwardly rectifying chloride channel in cultured hippocampal neurons. 771 38

The adenosine A2a receptor inhibition of potassium (15 mM)-evoked GABA release from striatal nerve terminals has been examined. High extracellular calcium concentrations (4 mM) reduced the effect of the A2a receptor agonist CGS-21680 (1 nM). CGS-21680 inhibited GABA release in the presence of the L-type calcium channel blocker nifedipine, which itself inhibited evoked GABA release (by 16 +/- 4%). omega-Conotoxin inhibited the evoked release by 45 +/- 4% and prevented the action of CGS-21680. Forskolin and 8-bromo cyclic AMP both stimulated evoked GABA release at low concentrations, but at higher concentrations they abolished the inhibition by CGS-21680 without affecting the evoked release. The nonselective protein kinase inhibitor H-7 inhibited both the evoked release and the inhibition by CGS-21680, whereas the selective protein kinase A and G inhibitor HA-1004 had no effect on either evoked release or the action of CGS-21680. Pretreatment with pertussis toxin did not affect the A2a receptor-mediated inhibition. Therefore, the effect of A2a receptor stimulation was not mediated by protein kinases A or G but was inhibited by elevated cyclic AMP levels and mimicked by inhibitors of the N-type calcium channel and protein kinase C.
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PMID:Inhibition of striatal GABA release by the adenosine A2a receptor is not mediated by increases in cyclic AMP. 776 61

We studied the effects of GABA on anoxia-induced injury in CNS white matter using optic nerves exposed to 60 min of anoxia. Injury was assessed by recording pre- and postanoxic compound action potentials (CAPs). GABA (1 microM) significantly increased postanoxic CAP recovery when applied 60 min prior to anoxia. This effect was bicuculline (100 microM) insensitive, mimicked by baclofen (1 microM), blocked by GABA-B antagonists, and not mimicked by selective GABA-A agonists. GABA therefore acted at GABA-B receptors. High concentrations of GABA and baclofen did not influence recovery, possibly indicating GABA-B receptor desensitization at high agonist concentrations. Pertussis toxin (PTX) treatment reduced postanoxic CAP recovery in the presence of 1 microM GABA to control levels, indicating the recruitment of a G-protein-linked intracellular pathway. Protein kinase C (PKC) activation with 12-myristate 13-acetate (PMA) mimicked the effects of GABA. Inhibition of PKC with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7) or staurosporine reduced postanoxic recovery in the presence of GABA to lower levels than under control conditions, confirming the involvement of PKC in the protective effect of GABA and indicating that this GABA-B receptor/G-protein/PKC protective pathway might be active under control conditions. This was confirmed by the observation that GABA-B receptor blockade, in the absence of exogenous GABA, significantly reduced postanoxia recovery. Thus, activation of the protective mechanism under control conditions is due to endogenous GABA release. Increasing the level of endogenous extracellular GABA by blocking GABA uptake with 1 mM nipecotic acid also protected against anoxia. We propose a model where release of GABA in white matter helps to limit nerve fiber injury during anoxia via recruitment of a G-protein/PKC pathway with subsequent phosphorylation of an unknown target protein.
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PMID:Endogenous GABA attenuates CNS white matter dysfunction following anoxia. 782 73

1. An in vitro slice preparation of rat amygdala was used to study the paired-pulse depression of the N-methyl-D-aspartate (NMDA) receptor-mediated synaptic potential e.p.s.p.NMDA. 2. The e.p.s.p.NMDA was isolated pharmacologically by applying a solution containing the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the gamma-aminobutyric acidA (GABAA) blocker picrotoxin and increasing the stimulus intensity. 3. When two stimuli of identical strength were applied in close succession, the second e.p.s.p.NMDA was depressed. This paired-pulse depression was seen with interstimulus intervals of between 100 ms and 2000 ms; the maximal depression was observed at interval of 200 ms. 4. Superfusion of phaclofen or 2-hydroxy-saclofen inhibited the paired-pulse depression indicating the involvement of GABAB receptors. 5. Bath applications of Ba2+ or intracellular injection of Cs+ to block post- but not presynaptic GABAB receptors failed to inhibit the paired-pulse depression (PPD). 6. Incubation of slices with pertussis toxin prevented the postsynaptic hyperpolarization induced by baclofen. The PPD of e.p.s.p.NMDA, however, was not affected by pertussis toxin treatment. 7. These results suggest that GABA released by the first stimulus acts on GABAB receptors to suppress the second e.p.s.p.NMDA via mechanisms other than activation of a postsynaptic GABAB receptor-coupled K+ conductance.
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PMID:Paired-pulse depression of the N-methyl-D-aspartate receptor-mediated synaptic potentials in the amygdala. 785 45


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