UMLS:C0043167 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using the membranes treated with Triton X-100, we studied the interaction between gamma-aminobutyric acid (GABA)B receptors and the GTP-binding proteins which are the substrates for ADP-ribosylation by the islet-activating protein (IAP), pertussis toxin. The addition of guanine nucleotides to the membranes markedly decreased the binding of GABA to GABAB receptors. Preincubation of the membranes with IAP plus NAD caused ADP-ribosylation of the 41,000- and 39,000-Da proteins selectively and decreased GABA binding to GABAB receptors in a time- and dose-dependent manner. This decrease of binding appeared to be due to the reduction of receptor affinity for agonist. The GTP-binding proteins which are ADP-ribosylated by IAP were purified from the membrane fraction of bovine cerebral cortex. The addition of the purified GTP-binding proteins to IAP-treated membranes restored the high affinity binding of GABA to GABAB receptor. The two GTP-binding proteins which were resolved by octyl-Sepharose column chromatography showed similar efficacy in restoring GABA binding. Thus, GABAB receptors are coupled to GTP-binding proteins, IAP-specific substrates, in the brain membranes.
...
PMID:Prevention of the agonist binding to gamma-aminobutyric acid B receptors by guanine nucleotides and islet-activating protein, pertussis toxin, in bovine cerebral cortex. Possible coupling of the toxin-sensitive GTP-binding proteins to receptors. 299 84

Treatment of membranes from bovine cerebral cortex with N-ethylmaleimide (NEM) resulted in inhibition of gamma-aminobutyric acid (GABA) binding to GABAB receptors. The binding curve for increasing concentrations of agonist was shifted to the right by NEM treatment. Guanine nucleotide had little effect on the binding of GABA to NEM-treated membranes. The addition of purified GTP-binding proteins, which were the substrates of islet-activating protein (IAP), pertussis toxin, to the NEM-treated membranes caused a shift of the binding curve to the left, suggesting modification of GTP-binding proteins rather than receptors by NEM. Therefore, the effect of NEM on two purified GTP-binding proteins, Gi (composed of three subunits with molecular weight of alpha, 41,000; beta, 35,000; gamma, 10,000) and Go (alpha, 39,000; beta, 35,000; gamma, 10,000) was studied. NEM did not significantly change guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) binding and GTPase activity of these two proteins. In contrast, NEM-treated Gi and Go were not ADP-ribosylated by IAP and did not increase GABA binding to NEM-treated membranes. When alpha and beta gamma subunits were treated with NEM and then mixed with nontreated alpha and beta gamma to form Gi or Go, respectively, both oligomers with NEM-treated alpha-subunits lost their abilities to be IAP substrates and to couple to receptors. These results indicate that NEM uncoupled GTP-binding proteins from receptors by modifying alpha-subunits of GTP-binding proteins, and the site seemed to be on or near the site of ADP-ribosylation by IAP. When alpha and beta gamma subunits were treated with NEM and then mixed to form Gi or Go, GTP gamma S binding in the absence of Mg2+ and GTPase activity were changed, although they were not affected when oligomers were treated with NEM. The results suggest the existence of another sulfhydryl group which is protected from NEM by the association of subunits. The modification of this sulfhydryl group by NEM appeared to interfere with the interaction between alpha and beta gamma.
...
PMID:Uncoupling of gamma-aminobutyric acid B receptors from GTP-binding proteins by N-ethylmaleimide: effect of N-ethylmaleimide on purified GTP-binding proteins. 300 32

We have previously demonstrated that gamma-aminobutyric acid (GABA) is a potent regulator of secretory and electrical activity in melanotrophs of the frog pituitary. The aim of the present study was to investigate the intracellular events which mediate the response of melanotrophs to GABA. We first observed that GABA (1-100 microM) inhibited both basal and forskolin-stimulated cyclic AMP (cAMP) formation. The inhibitory effect of GABA on cAMP levels was mimicked by the GABAB receptor agonist baclofen (100 microM) and totally abolished by a 4-h pretreatment with pertussis toxin (0.1 microgram/ml). In contrast, the specific GABAA agonist 3-aminopropane sulphonic acid (3APS) did not affect cAMP production. Both GABA and 3APS (100 microM each) induced a biphasic effect on alpha-MSH release from perifused frog neurointermediate lobes, i.e. a transient stimulation followed by an inhibition of alpha-MSH secretion. Administration of forskolin (10 microM) prolonged the stimulatory phase and attenuated the inhibitory phase evoked by GABA and 3APS, indicating that cAMP modulates the response of melanotrophs to GABAA agonists. Ejection of 3APS (1 microM) in the vicinity of cultured melanotrophs caused a massive increase in intracellular calcium concentration ([Ca2+]i). The stimulatory effect of 3APS on [Ca2+]i was abolished when the cells were incubated in a chloride-free medium. The formation of inositol trisphosphate was not affected by 3APS, suggesting that the increase in [Ca2+]i cannot be ascribed to mobilization of intracellular calcium stores. omega-Conotoxin did not alter the secretory response of frog neurointermediate lobes to 3APS, while nifedipine blocked the stimulation of alpha-MSH secretion induced by 3APS. In conclusion, the present data indicate that, in frog pituitary melanotrophs, (i) the stimulatory phase evoked by GABAA agonists can be accounted for by an influx of calcium through L-type calcium channels, (ii) the inhibitory effect evoked by GABAB agonists can be ascribed to inhibition of adenylate cyclase activity and (iii) cAMP attenuates the inhibitory phase evoked by GABAA agonists. Taken together, these data suggest that activation of GABAB receptors may modulate GABAA receptor function.
...
PMID:Mechanism of action of gamma-aminobutyric acid on frog melanotrophs. 777 33

In this study, we examined the response of spontaneously active as well as quiescent cells (L-glutamate-activated) in the rat medial prefrontal cortex (mPFc) to the iontophoresis of 2-methylserotonin (2-Me-5-HT, 5-HT3 receptor agonist), (+/-)-2,5-dimethoxy-(4-iodo-phenyl)-2-aminopropane (DOI, 5-HT2A,2C receptor agonist), 8-hydroxy-N,N-di-propylamino tetralin (8-OH-DPAT, 5-HT1A receptor agonist) and gamma-aminobutyric acid (GABA, a non-selective GABA receptor agonist) after the intracerebral administration of pertussis toxin, an inactivator of the Gi/o protein. This was accomplished using the techniques of extracellular single cell recording and iontophoresis. The administration of pertussis toxin (0.5 microgram, 24 hours before the experiment) into the mPFc did not alter the response of mPFc cells to the iontophoresis of DOI, 2-Me-5HT or GABA compared to saline treated controls. However, the response of mPFc cells to the iontophoresis of 8-OH-DPAT was significantly attenuated in the animals pretreated with pertussis toxin compared to controls. These results suggest that the 5-HT1A but not 5-HT2A,2C or 5-HT3 receptor is coupled to the Gi/o protein.
...
PMID:Effect of pertussis toxin on the response of rat medial prefrontal cortex cells to the iontophoresis of serotonin receptor agonists. 786 72

1. Whole cell voltage-clamp techniques were used in the CA1 region of rat hippocampal slices to study presynaptic and postsynaptic gamma-aminobutyric acid B (GABAB) response mechanisms. The effects of the protein kinase C activator phorbol 12,13-diacetate (PDA), barium (Ba2+), and pertussis toxin were compared on the presynaptic and postsynaptic GABAB actions of bath-applied baclofen and paired-pulse depression (PPD) of the monosynaptic GABAA inhibitory postsynaptic current (IPSC). The magnitude of PPD was dependent on the amplitude of the first response. PPD was predominantly a GABAB-mediated effect, as it was very much reduced by the GABAB antagonist CGP 35348. 2. PDA enhanced monosynaptic GABAA IPSCs through an apparently presynaptic mechanism. Iontophoretic GABAA responses were unaffected, and there was no change in EIPSC. PDA increased the frequency of spontaneous, tetrodotoxin-insensitive IPSCs without significantly affecting their amplitudes. The inactive phorbol ester, 4 alpha-PDA did not alter IPSCs. After PDA application, stimulus intensity was adjusted to produce responses of comparable amplitude to control responses. PDA had a marked and reversible depressant effect on the postsynaptic GABAB response and caused a lesser, but still significant, reduction in the baclofen-induced reduction of monosynaptic IPSCs. PDA had no effect on PPD. 3. Ba2+ dramatically reduced postsynaptic GABAB responses; it had no effect on PPD. Ba2+ tended to decrease the presynaptic baclofen reduction of IPSCs, although this was not statistically significant. 4. Pertussis toxin, injected 2-3 days earlier into the intact hippocampus, blocked all three GABAB responses equally (approximately 70% decrease). 5. We conclude that presynaptic and postsynaptic GABAB mechanisms are mediated by G proteins that couple to different mechanisms. Discrepancies with previous work are evidently due to the use of different tissue preparations and different target responses. Even though protein kinase C activation caused a partial reduction in the presynaptic effect of baclofen, its lack of effect on PPD makes a significant role for protein kinase C in modulation of PPD unlikely.
...
PMID:Differences between presynaptic and postsynaptic GABAB mechanisms in rat hippocampal pyramidal cells. 788 61

Somatostatin (SS) has both excitatory and inhibitory actions on myenteric cholinergic transmission, which are mimicked by gamma-aminobutyric acid (GABA). We hypothesized that both effects of SS are mediated by neural GABA pathways. In guinea pig ileal longitudinal muscle-myenteric plexus, SS evoked [3H]-GABA release verifying GABA neural activation. SS (10(-9)-10(-5) M) stimulation of atropine-sensitive ileal contraction and evocation of tetrodotoxin-sensitive [3H]acetylcholine (ACh) release was mimicked by the GABAA agonist muscimol but not the GABAB agonist baclofen. SS (10(-7) M)-evoked contraction and [3H]ACh release were markedly reduced by the GABAA antagonist bicuculline (10(-5) M) but not the GABAB antagonist phaclofen. Cholecystokinin (CCK) evokes ileal contraction via an atropine-sensitive pathway and stimulates ACh release via adenylate cyclase activation. SS inhibited contraction and release evoked by CCK (10(-7) M). These inhibitory actions were reversed by phaclofen but not bicuculline and were mimicked by baclofen but not muscimol. Pertussis toxin (200 ng/ml for 3 h) reversed the inhibitory effects of SS and baclofen on CCK-stimulated contraction and release. In conclusion, SS modulates ileal cholinergic pathways by stimulation of GABA neural pathways. The excitatory action of SS is mediated by GABAA receptors, whereas the inhibitory action utilizes GABAB receptors via a pertussis toxin-sensitive G protein.
...
PMID:GABA mediation of the dual effects of somatostatin on guinea pig ileal myenteric cholinergic transmission. 809 12

The purpose of the experiments was to examine the behavior of cytosolic Ca2+ ([Ca2+]i) in individual pituitary melanotrophs and how that is affected by physiological ligands that inhibit or stimulate melanotroph secretion. Melanotrophs were dispersed from neurointermediate lobes of Xenopus laevis adapted to a black background, and [Ca2+]i was measured with fura-2. In basal (unstimulated) conditions, repetitive transient elevations in [Ca2+]i, not hitherto observed in any melanotrophs, were detected in 73% of the cells. These cytosolic Ca pulses occurred at fairly regular intervals (1-10 min) and lasted from a half to several minutes, during which [Ca2+]i rose several-fold. Pulsing was promptly and reversibly arrested by the secreto-inhibitory transmitters, dopamine, neuropeptide-Y (NPY), and gamma-aminobutyric acid (GABA), and also by quinpirole, muscimol, and baclofen. Pertussis toxin eliminated the responses to dopamine, NPY, and GABAB receptor activation, but spared responses to GABAA receptor activation. The responses to the physiological inhibitors and to the Ca channel blocker Ni were close to all or nothing; a mere doubling of an ineffective concentration commonly sufficed to arrest pulsing. Submaximal responses, seen over a narrow concentration range, involved a slowing of the pulsing. Cells not pulsing spontaneously were responsive to dopamine, GABA, and NPY and pulsed in response to the secretagogues CRF and TRH. They are suggested to be melanotrophs not actively secreting. The behavior of [Ca2+]i parallels secretory activity and strengthens the view that spontaneous secretion is driven by spontaneous influx of Ca ions and that secreto-inhibitory transmitters act by suppressing this influx and lowering [Ca2+]i. Cytosolic Ca pulsing may provide an efficient means of sustaining a high rate of spontaneous secretion.
...
PMID:Spontaneous cytosolic calcium pulsing detected in Xenopus melanotrophs: modulation by secreto-inhibitory and stimulant ligands. 838 13

The injection of 1 microgram of pertussis toxin, which inactivates Gi/o proteins, in the rat dorsal raphe nearly abolished the responsiveness of serotonin (5-HT) neurons to microiontophoretic applications of 5-HT and selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) without altering their responsiveness to of gamma-aminobutyric acid (GABA). In contrast, the injection of 1 microgram of cholera toxin, which causes an activation of Gs proteins, did not alter the responsiveness of 5-HT neurons to 5-HT, 8-OH-DPAT or GABA. Such in situ injection of either toxin in the dorsal hippocampus decreased by about 90% the responsiveness of CA3 pyramidal neurons to microiontophoretic applications onto their cell body of 5-HT and 8-OH-DPAT, but not of GABA. The effectiveness of the stimulation of the ascending 5-HT pathway in suppressing the firing activity of the same neurons, which results from the release of 5-HT at the level of their dendritic tree, was also markedly decreased in the cholera toxin-treated rats, but intriguingly not in the pertussis toxin-treated rats. These results indicate that, on 5-HT neurons, the somato-dendritic 5-HT1A autoreceptor is coupled to Gi/o, but insensitive to the persistent activation of Gs proteins. In the CA3 region of the hippocampus, there would be two subsets of postsynaptic 5-HT1A receptors on the pyramidal neurons: those apposed to 5-HT terminals on their dendritic tree (denoted intrasynaptic) and those located on their cell body (denoted extrasynaptic). The former are cholera toxin sensitive, whereas the latter are sensitive to both pertussis and cholera toxins.
...
PMID:Differential properties of pre- and postsynaptic 5-hydroxytryptamine1A receptors in the dorsal raphe and hippocampus: II. Effect of pertussis and cholera toxins. 847 3

During embryogenesis, neuroblasts proliferate within germinal zones, then migrate to their final positions. Although many neurons migrate along radial glial fibers, evidence suggests that environmental factors, as yet unidentified, also influence neuroblast movement. In vivo, nerve growth factor (NGF) and gamma-aminobutyric acid (GABA) colocalize near target destinations of migratory neuroblasts. In vitro, embryonic spinal neurons migrate towards NGF and GABA (Behar et al.: J Neurosci 14:29-38, 1994), implying that the molecules may act as chemoattractants in vivo. Here, we have used an in vitro assay of migration to show that migratory responses to these attractants develop along a ventrodorsal gradient that parallels terminal mitosis during cord development, and that GABA stimulates chemokinesis (motility without a gradient) via heterogeneous receptors involving separate signalling pathways. Both GABAA (muscimol) and GABAB (baclofen) agonists mimicked the effects of GABA in stimulating chemokinesis. Muscimol-induced motility was only blocked by GABAA antagonists (bicuculline or picrotoxin), whereas migration to baclofen was blocked by antagonists of both GABAA and GABAB (2-hydroxysaclofen) receptors. Migration to baclofen, but not muscimol, was abolished in the presence of 8-bromo cAMP or pertussis toxin, indicating that the former, but not the latter, attractant may stimulate motility via Gi/Go GTP binding proteins, and that PKA may modulate migratory responses to baclofen. Migration to GABA was partially attenuated by each of the GABA receptor antagonists. These results lead us to conclude that the natural ligand stimulates neuroblast motility via heterogeneous receptors coupled to different signalling mechanisms.
...
PMID:GABA-induced motility of spinal neuroblasts develops along a ventrodorsal gradient and can be mimicked by agonists of GABAA and GABAB receptors. 853 Dec 31

The influence of the ATP-sensitive K+(KATP) channel opener cromakalim on the antinociception induced by agonists of several receptors coupled to pertussis toxin-sensitive G proteins, clonidine (alpha2 adrenoceptor), baclofen (gamma-aminobutyric acid(B) receptor), morphine (mu opioid receptor) and U50,488H (kappa opioid receptor), was evaluated with a tail-flick test in mice. The subcutaneous administration of clonidine (0.12-2 mg/kg), morphine (0.5-16 mg/kg), baclofen (2-16 mg/kg) and U50,488H (2-16 mg/kg) induced a dose-dependent antinociceptive effect. Cromakalim (8-64 microgram/mouse intracerebroventricularly [i.c.v.]) did not change tail-flick latency in control animals but produced a dose-dependent enhancement of the antinociception induced by clonidine and morphine, and shifted their dose-response curves to the left. These effects of cromakalim were antagonized dose dependently by the K(ATP) channel blocker gliquidone (0.1-8 microgram/mouse i.c.v.). On the other hand, cromakalim (16-64 microgram/mouse i.c.v.) did not significantly enhance the antinociception induced by baclofen and U50,488H and did not shift their dose-response curves. These results suggest that opening of the K(ATP) channels plays an important role in the antinociception mediated by alpha(2) adrenoceptors and mu opioid receptors, but not in that induced by gamma-aminobutyric acid(B) and kappa opioid receptors.
...
PMID:Cromakalim differentially enhances antinociception induced by agonists of alpha(2)adrenoceptors, gamma-aminobutyric acid(B), mu and kappa opioid receptors. 878 44

<< Previous 1 2 3 4 5 6 7 Next >>