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. Tight-seal, whole-cell recording was used to study GABAB receptor-mediated inhibition of spontaneous inhibitory synaptic currents in cultured rat midbrain neurones. 2. Spontaneous miniature inhibitory postsynaptic currents (mIPSCs) were recorded in tetrodotoxin (TTX), Cd2+ and Ba2+. (R)-(-)-baclofen reduced the frequency of mIPSCs through a presynaptic mechanism. The EC50 for this effect was 7 microM. It was antagonized by the GABAB receptor antagonist CGP55845A (0.5 microM). 3. In pertussis toxin (PTX)-treated cultures, some GABAB receptor-mediated reduction of the frequency of mIPSCs persisted. In contrast, PTX treatment totally abolished inhibition of miniature excitatory postsynaptic currents (mEPSCs). 4. In PTX-treated cultures, a saturating concentration of (R)-(-)-baclofen inhibited action potential-generated IPSCs but no EPSCs. 5. PTX treatment abolished the (R)-(-)-baclofen-mediated inhibition of high voltage-activated somatic Ca2+ currents and of spontaneous IPSCs depending on presynaptic Ca2+ entry. 6. We conclude that cellular mechanisms underlying GABAB receptor-mediated inhibition of mIPSCs contribute to auto-inhibition of GABA release.
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PMID:GABAB receptor-mediated inhibition of spontaneous inhibitory synaptic currents in rat midbrain culture. 916 88

Lysophosphatidic acid (LPA) is a simple phospholipid that can be released from thrombin-activated platelets and growth factor-activated fibroblasts. The effects of this lipid signaling molecule on membrane currents of cultured human retinal pigment epithelial (RPE) cells were investigated using whole cell recording techniques. Bath application of LPA evoked an inward current that was sometimes preceded by an outward current. The inward current reversed near 0 mV regardless of Cl- equilibrium potential and was suppressed by lowering extracellular [Na+] or application of Cd2+ (3 mM) suggesting that it is a non-selective cation current. The outward current reversed near the K+ equilibrium potential (EK) suggesting it is carried predominantly by K+ ions. The effects of LPA appear to be mediated by a receptor rather than non-specific detergent effects since: (a) both currents showed a similar saturating concentration/response relationship; (b) lysophosphatidylcholine, which has the same lipid tail as LPA, was significantly less effective than LPA in evoking inward currents; (c) LPA-evoked currents diminished with repeated applications of LPA suggesting receptor desensitization or washout of second messenger systems during whole cell recording; and (d) pertussis and cholera toxin pre-treatment suppressed the inward current, although not the outward current. Bath application of a calcium ionophore, ionomycin, stimulated an outward current which, like the LPA-sensitive current, reversed near EK. The results suggest that LPA stimulates one or more receptor subtypes which can associate with both a pertussis toxin-sensitive G protein resulting in generation of an inward cation current and a pertussis toxin-insensitive G protein resulting in generation of an outward current carried predominantly by K+.
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PMID:Lysophosphatidic acid stimulates two ion currents in cultured human retinal pigment epithelial cells. 923 59

1. The role of bradykinin receptors in the regulation of sympathetic transmitter release was investigated in primary cultures of neurones dissociated from superior cervical ganglia of neonatal rats. These cultures were loaded with [3H]-noradrenaline and the outflow of radioactivity was determined under continuous superfusion. 2. Bradykinin (100 nmol l[-1] applied for 10 min) caused a transient increase in tritium outflow that reached a peak within four minutes after the beginning of the application and then declined towards the baseline, despite the continuing presence of the peptide. ATP (100 micromol l[-1]) and nicotine (10 micromol l[-1]) caused elevations in 3H outflow with similar kinetics, whereas outflow remained elevated during a 10 min period of electrical field stimulation (0.5 ms, 50 mA, 50 V cm[-1], 1.0 Hz). 3. When bradykinin was applied for periods of 2 min, the evoked 3H overflow was half-maximal at 12 nmol l(-1) and reached a maximum of 2.3% of cellular radioactivity. The preferential B1 receptor agonist des-Arg9-bradykinin failed to alter 3H outflow. The B2 receptor antagonists, [D-Phe7]-bradykinin (1 micromol l[-1]) and Hoe 140 (10 nmol l[-1]), per se did not alter 3H outflow, but shifted the concentration-response curve for bradykinin-evoked 3H overflow to the right by a factor of 7.9 and 4.3, respectively. 4. Bradykinin-induced overflow was abolished in the absence of extracellular Ca2+ and in the presence of either 1 micromol l(-1) tetrodotoxin or 300 micromol l(-1) Cd2+, as was electrically-induced overflow. Activation of alpha2-adrenoceptors by 1 micromol l(-1) UK 14,304 reduced both bradykinin- and electrically-triggered overflow. The Ca2+-ATPase inhibitor thapsigargin (0.3 micromol l[-1]) failed to alter either type of stimulated overflow. Caffeine (10 mmol l[-1]) enhanced bradykinin-induced overflow, but reduced overflow triggered by electrical field stimulation. 5. Inclusion of Ba2+ (0.1 to 1 mmol l[-1]) in the superfusion medium enhanced electrically induced overflow by approximately 100% and potentiated bradykinin-triggered overflow by almost 400%. Application of 1 mmol l(-1) Ba2+ for periods of 2 min triggered 3H overflow, and this overflow was abolished by 1 micromol l(-1) tetrodotoxin and enhanced by 10 mmol l(-1) caffeine. In contrast, inclusion of tetraethylammonium (0.1 to 1 mmol l[-1]) in the superfusion buffer caused similar increases of bradykinin- and electrically evoked 3H overflow (by about 100%), and tetraethylammonium, when applied for 2 min, failed to alter 3H outflow. 6. Treatment of cultures with 100 ng ml(-1) pertussis toxin caused a significant increase in bradykinin-, but not in electrically-, evoked tritium overflow. Treatment with 100 ng ml(-1) cholera toxin reduced both types of stimulated 3H overflow. 7. These data reveal bradykinin as a potent stimulant of action potential-mediated and Ca2+-dependent transmitter release from rat sympathetic neurones in primary cell culture. This neurosecretory effect of bradykinin involves activation of B2-receptors, presumably linked to pertussis- and cholera toxin-insensitive G proteins, most likely members of the Gq family. Results obtained with inhibitors of muscarinic K+ (KM) channels, like caffeine and Ba2+, indicate that the secretagogue action of bradykinin probably involves inhibition of these K+ channels.
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PMID:Noradrenaline release from rat sympathetic neurones triggered by activation of B2 bradykinin receptors. 935 1

The actions of serotonin on rat basolateral amygdala neurons were studied with conventional intracellular recording techniques and fura-2 fluorimetric recordings. Bath application of 5-hydroxytryptamine (5-HT or serotonin) reversibly suppressed the excitatory postsynaptic potential in a concentration-dependent manner without affecting the resting membrane potential and neuronal input resistance. Extracellular Ba2+ or pertussis toxin pretreatment did not affect the depressing effect of 5-HT suggesting that it is not mediated through activation of Gi/o protein-coupled K+ conductance. The sensitivity of postsynaptic neurons to glutamate receptor agonist was unaltered by the 5-HT pretreatment. In addition, the magnitude of paired-pulse facilitation was increased in the presence of 5-HT indicating a presynaptic mode of action. The effect of 5-HT was mimicked by the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) and was blocked by the selective 5-HT1A antagonist 1-(2-methoxyphenyl)-4[4-(2-phthalimido)butyl]piperazine oxadiazol-3-yl]methyl]phenyl]-methanesulphonamide. In contrast, the selective 5-HT2 receptor antagonist ketanserin failed to affect the action of 5-HT. The effects of 5-HT and 8-OH-DPAT on the high K+-induced increase in [Ca2+]i were studied in acutely dissociated basolateral amygdala neurons. High K+-induced increase in [Ca2+]i was blocked by Ca2+-free solution and Cd2+ suggesting that Ca2+ entry responsible for the depolarization-evoked increase in [Ca2+]i occurred through voltage-dependent Ca2+ channels. Application of 5-HT and 8-OH-DPAT reduced the K+-induced Ca2+ influx in a concentration-dependent manner. The effect of 5-HT was completely abolished in slices pretreated with Rp-cyclic adenosine 3',5'-monophosphothioate (Rp-cAMP), a regulatory site antagonist of protein kinase A, suggesting that 5-HT may act through a cAMP-dependent mechanism. Taken together, these results suggest that functional 5-HT1A receptors are present in the excitatory terminals and mediate the 5-HT inhibition of synaptic transmission in the amygdala.
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PMID:Serotonin depresses excitatory synaptic transmission and depolarization-evoked Ca2+ influx in rat basolateral amygdala via 5-HT1A receptors. 975 2

The effects of histamine on high-voltage-activated Ca2+ channels in the histaminergic neurons acutely dissociated from the rat tuberomammillary nucleus were investigated in the nystatin-perforated patch recording mode under voltage-clamp conditions. Histamine suppressed the high-voltage-activated Ca2+ channel currents in neurons which were positive for histidine decarboxylase with immunocytochemistry. The half-maximum inhibitory concentration and maximum inhibition were 2.6 x 10(-7) M and 16.6+/-1.90%, respectively. An H3 receptor agonist, R(-)-alpha-methylhistamine, mimicked the response to histamine, and thioperamide, an H3 receptor antagonist, inhibited the response to histamine. On the other hand, neither 2-methylhistamine, an H1 receptor agonist, nor dimaprit, an H2 receptor agonist, had a significant effect on the Ca2+ channel currents. Pretreatment with pertussis toxin blocked the inhibitory effect of histamine on Ca2+ channels, suggesting the involvement of Gi/Go proteins in the action of histamine. Omega-conotoxin-GVIA, omega-agatoxin-IVA, nicardipine, and omega-conotoxin-MVIIC blocked the high-voltage-activated Ca2+ channel currents by 15.6, 4.3, 27.1, and 31.2% of the total current, respectively, suggesting the existence of N-, P-, L-, and Q-type Ca2+ channels. A current that was insensitive to these blockers was also found. This residual current, "R-type", was completely suppressed by the addition of 200 microM Cd2+. Histamine significantly inhibited both the N- and P-type current components among these five types of Ca2+ channel currents. We concluded that histamine suppresses the N- and P-type Ca2+ channels in histaminergic neurons through an H3 receptor which is linked to a pertussis toxin-sensitive G-protein.
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PMID:Histamine modulates high-voltage-activated calcium channels in neurons dissociated from the rat tuberomammillary nucleus. 975 67

ATP is a fast transmitter in sympathetic ganglia and at the sympathoeffector junction. In primary cultures of dissociated rat superior cervical ganglion neurons, ATP elicits noradrenaline release in an entirely Ca2+-dependent manner. Nevertheless, ATP-evoked noradrenaline release was only partially reduced (by approximately 50%) when either Na+ or Ca2+ channels were blocked, which indicates that ATP receptors themselves mediated transmembrane Ca2+ entry. An "axonal" preparation was obtained by removing ganglia from explant cultures, which left a network of neurites behind; immunostaining for axonal and dendritic markers revealed that all of these neurites were axons. In this preparation, ATP raised intraaxonal Ca2+ and triggered noradrenaline release, and these actions were not altered when Ca2+ channels were blocked by Cd2+. Hence, Ca2+-permeable ATP-gated ion channels, i.e., P2X purinoceptors, are located at presynaptic sites and directly mediate Ca2+-dependent transmitter release. These presynaptic P2X receptors displayed a rank order of agonist potency of ATP >/= 2-methylthio-ATP > ATPgammaS >> alpha,beta-methylene-ATP approximately beta,gamma-methylene-L-ATP and were blocked by suramin or PPADS. ATP, 2-methylthio-ATP, and ATPgammaS also evoked inward currents measured at neuronal somata, but there these agonists were equipotent. Hence, presynaptic P2X receptors resemble the cloned P2X2 subtype, but they appear to differ from somatodendritic P2X receptors in terms of agonist sensitivity. Suramin reduced depolarization-evoked noradrenaline release by up to 20%, when autoinhibitory mechanisms were inactivated by pertussis toxin. These results indicate that presynaptic P2X purinoceptors mediate a positive, whereas G-protein-coupled P2Y purinoceptors mediate a negative, feedback modulation of sympathetic transmitter release.
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PMID:ATP stimulates sympathetic transmitter release via presynaptic P2X purinoceptors. 988 May 94

Activation of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors in cerebellar granule cells during perforated-patch whole-cell recordings activated an inward current at negative voltages which was followed, after a delay, by the inhibition of an outward potassium current at voltages positive to -20 mV. The activated inward current was inwardly rectifying suggesting that the AMPA receptors were Ca2+-permeable. This was confirmed by direct measurements of intracellular calcium where Ca2+ rises were seen following AMPA receptor activation in Na+-free external solution. Ca2+ rises were equally large in the presence of 100 microM Cd2+ to block voltage-gated Ca2+ channels. Specific voltage-protocols, allowing selective activation of the delayed rectifier potassium current (KV) and the transient A current (KA), showed that kainate inhibited KV, but not to any great extent KA. The inhibition of KV was blocked by the AMPA receptor antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) and was no longer observed when the KV current was abolished with high concentrations of Ba2+. The responses to kainate were not altered by pre-treating the cells with pertussis toxin, suggesting that the AMPA receptor stimulation of the G-protein Gi cannot account for the effects observed. Replacing extracellular Na+ with choline did not alter the inhibition of KV by kainate, however, removing extracellular Ca2+ reduced the kainate response. The inhibition of KV by kainate was unaffected by the presence of 100 microM Cd2+. The guanylyl cyclase inhibitor, ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), did not alter kainate inhibition of KV. It is concluded that ion influx (particularly Ca2+ ions) through AMPA receptor channels following receptor activation leads to an inhibition of KV currents in cerebellar granule neurons.
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PMID:Inhibition of delayed rectifier K+ conductance in cultured rat cerebellar granule neurons by activation of calcium-permeable AMPA receptors. 1076 23

Cytosolic free calcium, [Ca(2+)](i), measured in individual prothoracic gland cells of Manduca sexta with Fura-2 was increased by prothoracicotropic hormone, PTTH, and by mastoparan, a wasp venom peptide, activating G proteins. The effect on [Ca(2+)](i) of mastoparan and of PTTH was inhibited by cadmium and the antagonist of T-type calcium channels, amiloride, and not influenced by the L-type calcium channel blocker nitrendipine, suggesting that the same or similar plasma membrane channels are involved in the action of mastoparan and of PTTH. Pertussis toxin prevented the mastoparan-induced increase of [Ca(2+)](i), whereas the effect of PTTH is not influenced by pertussis toxin. Intracellular addition of GDP-beta-S failed to inhibit the PTTH-stimulated increase in [Ca(2+)](i) suggesting that G proteins are not involved in the stimulatory mechanism of PTTH.
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PMID:Pharmacological study of signal transduction during stimulation of prothoracic glands from Manduca sexta. 1087 67

1. The effects of cannabinoid (CB) receptor stimulation on membrane currents in single cells from the Syrian hamster vas deferens cell line DDT1MF-2 were investigated using the whole cell patch clamp technique. 2. The CB receptor agonist CP55,940 evoked a concentration-dependent transient outward current. The selective CB1 receptor ligand SR141716 (1 microM), but not the selective CB2 receptor ligand SR144528 (1 microM), inhibited the outward current. Pertussis toxin (100 ng ml-1 for 20 h) completely abolished the outward current. 3. Western blotting with an antibody against the rat (r)CB1 receptor showed a band characteristic for the CB1 receptor around 63 kDa in DDT1MF-2 cells. 4. The reversal potential for the outward current measured using a voltage ramp protocol was -84 +/- 5 mV. The current was inhibited by the Ca2+-dependent K+ channel blockers iberiotoxin (10 nM) and charybdotoxin (10 nM). 5. Removal of Ca2+ from the bathing solution, or the addition of 0.1 mM Cd2+ completely abolished the outward current evoked by 10 microM CP55,940. 6. The sarcoplasmic Ca2+ pump inhibitor thapsigargin reduced the outward current evoked by 10 microM CP55,940 in a concentration-dependent manner. 7. The mitogen-activating protein kinase (MAP kinase) inhibitor PD98059, but not the phospholipase C inhibitor U73122, inhibited the outward current evoked by 10 microM CP55,940. 8. The adenylyl cyclase inhibitor SQ22,536 (100 microM) and 8-Br-cyclic AMP (10 microM) significantly reduced the outward current evoked by 10 microM CP55,940. 9. Our data suggest that CB1 receptor stimulation in DDT1MF-2 cells leads to activation of a large conductance Ca2+-dependent K+ channel through a Gi/Go protein-mediated rise in [Ca2+]i, for which both inhibition of adenylyl cyclase and activation of MAP kinase are required. In addition, the cannabinoid-induced increase in [Ca2+]i is likely to arise from capacitive Ca2+ entry.
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PMID:Signal transduction of cannabinoid CB1 receptors in a smooth muscle cell line. 1117 94

The mechanism of calcium-independent spontaneous GABA release in a long-living (3-10 weeks) rat hippocampal neuron culture was studied. It was found that Cd2+ (100 microM), a Ca2+ channel blocker, reversibly decreased the frequency and amplitude of GABAergic spontaneous miniature inhibitory postsynaptic currents (smIPSCs). Besides, Cd2+ decreased the currents evoked by muscimol application onto the neurons, which is evidence of an additional postsynaptic effect. The GABAB receptor agonist baclofen (0.1-50 microns) produced a concentration-dependent decrease in the smIPSC frequency, while not affecting the current amplitude. The baclofen effect was blocked by the pertussis toxin. The baclofen efficacy both in the presence of Cd2+ (presumably compete blocking of Ca2+ channels) and in the absence of this agent were similar and could be completely accounted for by the loss of an equivalent smIPSC fraction. Thus, the presynaptic baclofen-induced inhibition of the spontaneous GABA release can be entirely independent of the calcium channel modulation (the latter playing a decisive role in a mediator release induced by the action potential). Therefore, the smIPSC measurements (widely used in the past decade for the study of presynaptic drug activity) may inadequately reflect the drug effect in the intact brain.
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PMID:[Calcium-independent inhibition of the spontaneous release of GABA by baclofen in the rat hippocampus]. 1154 95


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