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)

Dexmedetomidine, a highly selective and potent agonist at alpha-2 adrenoceptors, produces a hypnotic-anesthetic action in rats. The mechanism for this response may involve an inhibitory G-protein and increased conductance through a potassium channel. To investigate this, the effects of pertussis toxin, a specific inactivator of inhibitory G-proteins, and 4-aminopyridine, a blocker of potassium channels, on the hypnotic-anesthetic response to dexmedetomidine were studied in rats. Pertussis toxin and 4-aminopyridine both decreased the hypnotic-anesthetic action of dexmedetomidine in a dose-dependent fashion. To preclude the possibility that pertussis toxin and 4-aminopyridine attenuated the hypnotic-anesthetic action of dexmedetomidine via indirect central nervous system excitation, the effects of pertussis toxin and 4-aminopyridine on the hypnotic-anesthetic action of pentobarbital also were assessed. Pentobarbital-induced hypnosis was not attenuated by either treatment. These results suggest that the receptor-effector mechanism for the hypnotic-anesthetic action of dexmedetomidine involves an inhibitory G-protein and increased conductance through a potassium channel.
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PMID:Pertussis toxin and 4-aminopyridine differentially affect the hypnotic-anesthetic action of dexmedetomidine and pentobarbital. 197 96

Fetal rat dorsal root ganglion neurons (7-8 days in culture) were labeled with [3H]arachidonic acid for 24 h. Stimulation with 10 microM bradykinin (BK) for 30 s resulted in nearly 2-fold increases in levels of radioactive diglyceride and arachidonic acid. A similar result was obtained in the absence of receptor stimulation using the Ca2+ channel agonist BAY K 8644 (10 microM, in the presence of 100 mM potassium chloride) or the Ca2+ ionophore, ionomycin (2.5 microM). If Ca2+ influx was inhibited by adding 3 mM Co2+, a blocker of voltage-sensitive calcium channels, or 2.5 mM EDTA, then BK-stimulated accumulation of both arachidonate and diglyceride was inhibited. These data suggest Ca2+ influx is required for ligand-stimulated accumulation of both arachidonate (a product of diglyceride-lipase or phospholipase A2) and diglyceride (a product of phospholipase C). Two distinct populations of channels may be involved in these reactions since pretreatment with 10 microM nifedipine or 50 microM verapamil (agents which block a subset of voltage-sensitive Ca2+ channels) inhibited BK-stimulated accumulation of arachidonic acid, but did not inhibit diglyceride accumulation. Such functional discrimination appears to have physiological importance; the inhibitory effect of nifedipine and verapamil on BK-stimulated arachidonate release was mimicked by pretreatment with peptides which decrease Ca2+ channel conductance in dorsal root ganglion neurons. The three peptides used were 1 microM neuropeptide Y, 10 microM somatostatin, and 10 microM [N-MePhe3,D-Pro4]-morphiceptin. The effect of neuropeptide Y was blocked by pretreatment with pertussis toxin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation by neuropeptides of bradykinin-stimulated second messenger release in dorsal root ganglion neurons. 197 11

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. Whole-cell recordings were made from submucosal neurones acutely dissociated from guinea-pigs. The actions of noradrenaline, somatostatin and [Met5]enkephalin on currents carried by calcium ions were studied. 2. On depolarization from a holding potential of -70 mV, an inward current activated at -40 mV, reached its peak amplitude at 10 mV and reversed to outward at 72 mV (with external calcium of 5 mM and internal caesium of 160 mM). 3. Cadmium, nickel and cobalt reversibly blocked the calcium current; concentrations causing 50% block were 2.5, 500 and 2000 microM respectively. The calcium current (holding at -70 or -30 mV) was reversibly blocked by omega-conotoxin (100 nM), and unaffected by Bay K 8644 (0.1-10 microM) and nifedipine (1 microM). Cadmium caused an outward shift in holding current at -30 mV, implying that there was a persistent inward calcium current at this potential. 4. Noradrenaline, somatostatin and [Met5]enkephalin decreased the calcium current. The maximal inhibition observed with any one agonist, or with a combination of two agonists, did not exceed 50%; concentrations giving half-maximal inhibition were 5.5 microM for noradrenaline, 4 nM for somatostatin and 1 microM for [Met5]enkephalin. The inhibition was independent of membrane potential. All three agonists also reduced the persistent calcium current at -30 mV. 5. Inhibition of the calcium current by noradrenaline occurred with a latency of not less than 175 ms; cadmium applied by the same method depressed the current within 5-45 ms. 6. Experiments with selective agonists and antagonists indicated that the receptor types involved in calcium current inhibition were alpha 2-adrenoceptors and delta-opioid receptors. Somatostatin acted at a distinct receptor. 7. Calcium currents were also inhibited by intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S). Agonists were ineffective in cells pre-treated with pertussis toxin, but their action was restored when purified GTP-binding proteins (Go or Gi) were included in the intracellular recording solution. 8. It is concluded that noradrenaline, somatostatin and [Met5]enkephalin act at their respective receptors on guinea-pig submucosal neurones to inhibit a voltage-dependent calcium current. Activation of the same receptors also increases a potassium conductance in these cells: in both cases a pertussis-sensitive G protein is involved.
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PMID:Inhibition of calcium currents by noradrenaline, somatostatin and opioids in guinea-pig submucosal neurones. 198 21

1. Intracellular recordings were made from submucosal neurones of the guinea-pig ileum. The actions of noradrenaline, somatostatin and [Met5]enkephalin on nicotinic synaptic potentials (EPSPs) were studied. 2. In one series of experiments, agonists were applied by superfusion; noradrenaline (0.1-20 microM) decreased EPSP amplitude by 95-100% in all neurones. Similar application of somatostatin (1-100 nM) inhibited EPSPs in about half the neurones by a maximum of 40%. [Met5]enkephalin (0.1-10 microM) did not alter EPSPs. Idazoxan and yohimbine competitively antagonized the action of noradrenaline with dissociation equilibrium constants of 20 and 30 nM respectively. 3. In another series of experiments, noradrenaline and somatostatin were applied locally from a pipette so that they reached presynaptic terminals but not the cell bodies or axons of the presynaptic cell: noradrenaline inhibited EPSPs by 90% in all neurones but somatostatin had no effect. When applied locally to the cell bodies giving rise to the presynaptic fibres, both agonists inhibited EPSPs in half the neurones by 40%. 4. When noradrenaline was applied locally to presynaptic terminals, the latency to onset of noradrenaline to inhibit EPSPs was 45-160 ms; cadmium applied similarly depressed EPSPs in 5-50 ms. 5. Pertussis toxin pre-treatment only partially blocked presynaptic inhibition caused by noradrenaline but abolished the reduction of EPSP amplitude by somatostatin. 6. It is concluded that noradrenaline and somatostatin reduce the amplitude of the fast EPSP because they hyperpolarize cell bodies and prevent action potential initiation. Noradrenaline, but not somatostatin, has an additional action to inhibit acetylcholine release by acting at nerve terminal receptors. 7. The presynaptic inhibitory action of noradrenaline results from activation of alpha 2-adrenoceptors at nerve terminals but the mechanism(s) by which these presynaptic receptors act cannot be explained adequately by either activation of a potassium conductance and/or inhibition of a calcium conductance.
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PMID:Mechanisms underlying presynaptic inhibition through alpha 2-adrenoceptors in guinea-pig submucosal neurones. 198 22

To elucidate mechanisms of mercury toxicity, the cell membrane potential has been determined continuously in cultured kidney (MDCK)-cells during reversible application of mercury ions to extracellular perfusate. Exposure of the cells to 1 microM mercury ions is followed by rapid, sustained, and slowly reversible hyperpolarization of the cell membrane, increase of cell membrane potassium selectivity, and decrease of cell membrane resistance. Thus, mercury ions enhance the potassium conductance of the cell membrane. Half maximal hyperpolarizing effect is elicited by approximately 0.2 microM. Higher concentrations of mercury ions (greater than 10 microM) eventually depolarize the cell membrane. At extracellular calcium activity reduced to less than 0.1 microM, 1 microM mercury ions still leads to a sustained hyperpolarization and increase of potassium selectivity of the cell membrane. As evident from fluorescence measurements, 10 microM, but not 1 microM mercury ions leads to a rapid increase of intracellular calcium activity. Pretreatment of the cells with either pertussis toxin or cholera toxin does not blunt the hyperpolarizing effect of mercury ions. In conclusion, mercury ions activate the potassium conductance by a mechanism independent of increase of intracellular calcium activity and of cholera toxin- or pertussis toxin-sensitive G-proteins. This activation of potassium conductance may account for early effects of mercury intoxication, such as kaliuresis.
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PMID:Activation of cell membrane potassium conductance by mercury in cultured renal epithelioid (MDCK) cells. 199 17

Progesterone causes natriuresis, an effect largely attributed to displacement of aldosterone from its receptor. The present study, however, demonstrates that progesterone (0.1, 1, and 10 mumol/1, respectively) also causes a rapid, fully reversible depolarization of Madin-Darby canine kidney (MDCK) cells (by 1.3 +/- 0.5, 4.1 +/- 0.7 and 12.3 +/- 1.5 mV, respectively). 17 alpha-Hydroxyprogesterone and dihydroxytestosterone are, by two orders of magnitude, less effective, whereas cholesterol, aldosterone, hydrocortisone, and estradiol (each up to 10 mumol/l) did not significantly alter the potential difference across the cell membrane. The effect of progesterone is blunted by antiprogestogen RU 486 (5 mumol/l). The progesterone-induced depolarization is paralleled by a decrease of potassium selectivity and an increase of cell membrane resistance and is abolished in the presence of the potassium channel blocker barium (10 mmol/l), as well as in the presence of 40 mmol/l potassium in the extracellular fluid. Neither removal of extracellular chloride or bicarbonate nor amiloride, ouabain, or pretreatment with pertussis toxin abolish the depolarizing effect of 5 mumol/l progesterone. In conclusion, acute administration of progesterone depolarizes MDCK cells by decreasing the potassium conductance of the cell membrane.
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PMID:Progesterone inhibits K conductance in plasma membrane of cultured renal epitheloid MDCK cells. 203 30

1. Intracellular recordings were obtained from submucous plexus neurones of the guinea-pig caecum. 2. The resting membrane conductance displayed two types of inward rectification: one which developed at potentials more negative than -70 mV, and another that occurred at potentials more negative than the potassium equilibrium potential. The former inward rectification was blocked by extracellular caesium (Cs+; 1-2 mM) and the latter was blocked by Cs+ (1-2 mM) or barium (Ba2+; 30-100 microM). 3. The noradrenaline-induced current measured by subtraction of the current-voltage (I-V) relation before and after adding the agonist also showed an inward rectification around the resting potential. Ba2+ (30-100 microM) blocked both the outward and inward current induced by noradrenaline. The noradrenaline current was not affected by Cs+ (1-2 mM). Both the slow IPSP and the slow IPSC (inhibitory postsynaptic current) were reduced by Ba2+, but not by Cs+. 4. During the intracellular injection of guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S), multiple repetitive stimulation or repeated applications of noradrenaline produced irreversible membrane hyperpolarizations with a decreased membrane input resistance, until the membrane had approached the potassium equilibrium potential. 5. Pertussis toxin (1-40 micrograms/ml) abolished both the slow IPSP and the noradrenaline hyperpolarization without affecting the nicotinic fast EPSP or the slow EPSP. 6. Superfusion with a Ca(2+)-free, high-Mg2+ (12 mM) solution caused a membrane depolarization associated with an increased input resistance. It eliminated the Ca2+ spikes, the slow after-hyperpolarizations following the spikes, and the synaptic potentials within 3 min. Prolonged exposure (longer than 20 min) to this solution resulted in a progressive decline of the noradrenaline hyperpolarization. 7. Intracellular injection of ethylene glycol-bis(beta-aminoethylether)N,N,N',N'-tetraacetic acid (EGTA) reduced the slow IPSP and the noradrenaline hyperpolarization. Superfusion with a membrane-permeable Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester (BAPTA/AM; 10-200 microM) reduced the noradrenaline hyperpolarization. 8. Procaine reversibly reduced the slow IPSP and noradrenaline hyperpolarization without affecting the fast EPSP or slow EPSP at concentrations up to 300 microM.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanisms underlying intracellular signal transduction of the slow IPSP in submucous neurones of the guinea-pig caecum. 206 48

Using the patch-clamp technique, we studied regulation of potassium channels by G protein activators in the histamine-secreting rat basophilic leukemia (RBL-2H3) cell line. These cells normally express inward rectifier K+ channels, with a macroscopic whole-cell conductance in normal Ringer ranging from 1 to 16 nS/cell. This conductance is stabilized by including ATP or GTP in the pipette solution. Intracellular dialysis with any of three different activators of G proteins (GTP gamma S, GppNHp, or AlF-4) completely inhibited the inward rectifier K+ conductance with a half-time for decline averaging approximately 300 s after "break-in" to achieve whole-cell recording. In addition, with a half-time averaging approximately 200 s, G protein activators induced the appearance of a novel time-independent outwardly rectifying K+ conductance, which reached a maximum of 1-14 nS. The induced K+ channels are distinct from inward rectifier channels, having a smaller single-channel conductance of approximately 8 pS in symmetrical 160 mM K+, and being more sensitive to block by quinidine, but less sensitive to block by Ba2+. The induced K+ channels were also highly permeable to Rb+ but not to Na+ or Cs+. The current was not activated by the second messengers Ca2+, inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, or by cyclic AMP-dependent phosphorylation. Pretreatment of cells with pertussis toxin (0.1 microgram/ml for 12-13 h) prevented this current's induction both by guanine nucleotides and aluminum fluoride, but had no effect on the decrease in inward rectifier conductance. Since GTP gamma S is known to stimulate secretion from patch-clamped rat peritoneal mast cells, it is conceivable that K+ channels become inserted into the plasma membrane from secretory granules. However, total membrane capacitance remained nearly constant during appearance of the K+ channels, suggesting that secretion induced by GTP gamma S was minimal. Furthermore, pertussis toxin had no effect on secretion triggered by antigen, and triggering of secretion before electrical recording failed to induce the outward K+ current. Finally, GTP gamma S activated the K+ channel in excised inside-out patches of membrane. We conclude that two different GTP-binding proteins differentially regulate two subsets of K+ channels, causing the inward rectifier to close and a novel K+ channel to open when activated.
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PMID:G protein control of potassium channel activity in a mast cell line. 210 71

1. Bull-frog dorsal root ganglion cells in primary culture were voltage clamped in the whole-cell configuration. The pipette solution contained ATP (5 mM). 2. Step depolarizations (5-70 mV, 0.1-1 s) from a holding potential close to the resting potential (range, -64 to -79 mV) evoked a non-inactivating potassium current with properties indistinguishable from those which have been reported for the M-current of bull-frog sympathetic neurones. 3. An unhydrolysable ATP analogue APP(NH)P (5 mM), substitute with ATP in the pipette solution, did not support the M-current activation. 4. Bath application of ATP (30 nM-30 microM) reduced the amplitude of the M-current in a concentration-dependent manner, congruent to 50% inhibition of the current occurring with 1 microM-ATP. The main effect of ATP was to reduce the maximum M-conductance without changing the activation and deactivation kinetics of the M-current. 5. Essentially the same results were obtained with ADP (0.1-30 microM) and alpha, beta-methylene-ATP (10-30 microM). AMP (10-100 microM) and adenosine (10-30 microM) were without effect on the M-current. 6. The ATP-induced inhibition of the M-current was irreversible when an unhydrolysable GTP analogue GTP-gamma-S (10-30 microM) was present in the pipette solution. ATP (3 microM) reduced the amplitude of the M-current only by about 10% when GDP-beta-S (100 microM) was present in the pipette solution. Pre-treatment of the cells with pertussis toxin (IAP; 500 ng ml-1) for 24 h at 24 degrees C did not prevent the ATP-induced M-current inhibition. 7. Phorbol 12-myristate 13-acetate (PMA; 1-3 microM) reduced the amplitude of the M-current to about 50%. A reduction in the M-current amplitude by PMA (3 microM) and ATP (10 microM) was attenuated when staurosporine (200 nM) was present in the pipette solution. Forskolin (10 microM) was without effect on the M-current. 8. It is concluded that ATP acting at P2 receptors, associated with an IAP-insensitive GTP-binding protein, inhibits the M-current in amphibian primary afferent neurones.
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PMID:ATP regulates muscarine-sensitive potassium current in dissociated bull-frog primary afferent neurones. 212 60


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