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

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

The actions of agonists at alpha 2-adrenoceptors were investigated on single cells of the submucous plexus of the guinea pig small intestine. Intracellular recordings were made from neurons in vitro, and noradrenaline and other agonists were applied by adding them to the superfusion solution. The actions of noradrenaline released from terminals of sympathetic nerves was also studied by stimulating the nerves and recording the inhibitory postsynaptic current; this current can be mimicked by brief applications of noradrenaline from a pipette tip positioned within 50 micron of the neuron. The alpha 2-adrenoceptor-bound noradrenaline with an apparent dissociation constant of 15 microM, determined by the method of partial irreversible receptor inactivation: clonidine and 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14304) had dissociation constants of 36 nM and 2.5 microM respectively. Noradrenaline and UK 14304 caused maximal hyperpolarizations, or outward currents; clonidine was a full agonist in only 4 of 35 cells, a partial agonist in 25 cells, and without effect in 4 cells. Clonidine acted as a competitive antagonist of noradrenaline in those cells in which it lacked agonist action; its dissociation equilibrium constant determined by Schild analysis was about 20 nM. The potassium conductance increased by the alpha 2-adrenoceptor agonists, whether they were applied exogenously or released by stimulation of presynaptic nerves, showed marked inward rectification. The neurons showed inward rectification also in the absence of agonist; both types of rectification were eliminated by rubidium (2 mM), barium (3-30 microM) and caesium (2 mM). When the recording electrodes contained the nonhydrolysable derivative of guanosine 5'-triphosphate (GTP), guanosine 5'-O-(3-thiotriphosphate, GTP-gamma-S), the effects of applied alpha 2-adrenoceptor agonists did not reverse when they were washed from the tissue, implying that GTP hydrolysis is necessary for the termination of agonist action. Pretreatment with pertussis toxin abolished the inhibitory synaptic potential (IPSP) and agonist-induced hyperpolarizations. Phorbol 12,13-dibutyrate, forskolin, cholera toxin and sodium fluoride did not affect the responses to alpha 2-adrenoceptor agonists. The synaptic hyperpolarization resulting from sympathetic nerve stimulation, or the hyperpolarization evoked by a brief (3-5 ms) application of noradrenaline, began after a latency of about 30 and 60 ms respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanism of synaptic inhibition by noradrenaline acting at alpha 2-adrenoceptors. 290 Nov 10

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

1. The actions of serotonin (5-HT) on pyramidal cells of the CA1 region of the rat hippocampus were characterized using intracellular recording in in vitro brain slices. 2. 5-HT typically evokes a biphasic response consisting of a hyperpolarization which is followed by a longer-lasting depolarization. These effects on membrane potential are accompanied by a decrease in the calcium-activated after-hyperpolarization (a.h.p). 3. Detailed analysis using 5-HT antagonists and agonists indicates that the hyperpolarization is mediated by a 5-HT1A receptor. Spiperone is the most effective antagonist of the response and the selective 5-HT1A agonist, 8-OHDPAT, behaves as a partial agonist at this receptor. In agreement with the distribution of 5-HT1A binding sites, responses to 5-HT were most prominent in the stratum radiatum. 4. The hyperpolarizing response is associated with a decrease in input resistance, is blocked by extracellular barium and intracellular caesium, is unaffected by the chloride gradient, and its reversal potential shifts with the extracellular concentration of potassium as predicted for a response mediated by a selective increase in potassium permeability. 5. The depolarizing response and reduction in the a.h.p. could be studied in isolation by blocking the hyperpolarizing response with either pertussis toxin or spiperone. The pharmacology of these responses did not correspond to that of any of the 5-HT binding sites reported in C.N.S. tissue. Although the depolarization and blockade of the a.h.p. have the same time course it is unclear if they are mediated by the same or different receptors. 6. The depolarization most likely results from a decrease in resting potassium conductance. However, neither a blockade of the M current nor the a.h.p. current can account for the depolarization. 7. Blockade of phosphodiesterase activity by 3-isobutyl-1-methylxanthine (IBMX) did not enhance the depressant action of 5-HT on the a.h.p., making it unlikely that this action is mediated by cyclic AMP. 8. Blockade of the a.h.p. by 5-HT reduces spike frequency adaptation and counteracts the inhibitory action of 5-HT on 5-HT1A receptors. This excitatory action outlasts the hyperpolarizing action. 9. In summary 5-HT acts on at least two distinct receptors on hippocampal pyramidal cells, one coupled to the opening of potassium channels and a second coupled to a decrease in a resting potassium conductance and a decrease in the a.h.p.
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PMID:Pharmacologically distinct actions of serotonin on single pyramidal neurones of the rat hippocampus recorded in vitro. 344 77

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.
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PMID:Differences between presynaptic and postsynaptic GABAB mechanisms in rat hippocampal pyramidal cells. 788 61

Calcium, strontium and barium induced an exocytotic response in electropermeabilized rabbit neutrophils while magnesium was without any effect. The extent of enzyme release was found to depend upon the concentration of these cations. For all cations, an optimum concentration was found with the same maximum enzyme release. At concentrations higher than optimum a decrease in lysozyme release was observed. Efficiency to induce enzyme release was in the order: Ca2+ > Sr2+ > Ba2+. Enzyme release was significantly enhanced by guanosine-5'-[gamma-thio]triphosphate (GTP gamma S) resulting in a shift to the left of the dose/response curve. The enhancement by GTP gamma S was strongest with Ca2+, was less with Sr2+, and was very little with Ba2+. The time course of lysozyme release was the same for Ca2+, Sr2+, and Ba2+ in the presence and absence of GTP gamma S when suboptimal cation concentrations were used. A decrease in responsiveness to the effectors after electropermeabilization was observed with Ca2+, Sr2+ and Ba2+ in the presence and absence of GTP gamma S. The lysozyme release induced by the different cations was not inhibited by the protein kinase C inhibitor staurosporine and was slightly affected by pertussis toxin. Ca2+ and Sr2+, but not Ba2+, potentiated formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe) induced enzyme release in intact neutrophils. The divalent cation ionophore A23187 induced enzyme release in the presence of Ca2+ and Sr2+ but not in the presence of Ba2+. The results obtained with electropermeabilized neutrophils indicate that Sr2+ and Ba2+ can act as substitutes for Ca2+ in activating exocytosis, and that permeabilized neutrophils provide the best tool to investigate the effects of alkaline earth ions in exocytosis.
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PMID:Strontium and barium induce exocytosis in electropermeabilized neutrophils. 841 94

Human D2, D3, D4 and dopamine receptors were individually coexpressed in Xenopus oocytes with a G protein-regulated inwardly rectifying potassium channel (GIRK1). At -100 mV in 96 mM potassium, dopamine (0.1-100 nM) evoked an inward current; the current showed inward rectification, reversed polarity at 0 mV, and was blocked by barium (50% inhibition by 10 microM). The concentrations of dopamine activating 50% of the maximal current (EC50) were not different (2-4 nM) for D2, D3, and D4 receptors, but the maximal current was 3-fold larger for D2 and D4 than for D3 receptors. Dopamine evoked reproducible inward currents at D2 and D4 receptors when applied repeatedly, but second responses could not be observed in oocytes expressing D3 receptors. 7-Hydroxy-N,N-di-n-propyl-2-aminotetralin mimicked the effect of dopamine (EC50 of approximately 2, approximately 3, and approximately 19 nM at D2, D3, and D4, respectively). (-) Sulpiride reversibly blocked the dopamine-induced current with IC50 values of 5, 300, and 2000 nM for D2, D3, and D4 receptors, respectively. Dopamine was ineffective in oocytes injected 2 hr previously with pertussis toxin. We concluded that all three D2-like dopamine receptors share the potential to activate inwardly rectifying potassium channels.
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PMID:D2, D3, and D4 dopamine receptors couple to G protein-regulated potassium channels in Xenopus oocytes. 860 93

It has been previously demonstrated that activation of A1 adenosine receptors in frog melanotrophs causes inhibition of spontaneous action potential discharges and alpha-melanocyte-stimulating hormone secretion. In the present study, we have investigated the effect of adenosine on high-voltage-activated (HVA) calcium currents in cultured melanotrophs, using the whole-cell variant of the patch-clamp technique with barium as a charge carrier. Adenosine and the specific A1 adenosine receptor agonist R-PIA (50 microM each) produced a decrease of the amplitude of the barium current, while the selective A2 adenosine receptor agonist CGS 21680 did not affect the current. The inhibitory effect of R-PIA was observed throughout the activation range of the current, with stronger responses at more positive potentials. R-PIA inhibited both the L- and N-type components of the current, the effect on the N-component being two-fold higher than on the L-component. The inhibitory effect of R-PIA was rendered irreversible by addition of GTP gamma S (100 microM) to the intracellular solution. Pre-treatment of the cells with pertussis toxin (1 microgram/ml; 12 h) totally abolished the effect of R-PIA on the HVA calcium channels. Conversely, addition of a high concentration of cAMP (100 microM) together with the phosphodiesterase inhibitor IBMX (100 microM) to the intracellular solution did not modify the effect of R-PIA on the current. It is concluded that, in frog melanotrophs, adenosine induces inhibition of L- and N-calcium currents and that this effect is mediated by a pertussis toxin-sensitive G protein. Our data also indicate that the inhibitory effect of adenosine on the calcium currents is not mediated by inhibition of adenylyl cyclase.
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PMID:Adenosine inhibits L- and N-type calcium channels in pituitary melanotrophs. Evidence for the involvement of a G protein in calcium channel gating. 886 54

We characterized whole cell barium currents through calcium channels and investigated the effects of serotonin (5-HT) on calcium channel currents and firing behavior in visualized caudal raphe neurons of the neonatal rat in brain stem slices (n = 201). A subpopulation of recorded neurons was recovered after staining for tryptophan hydroxylase (TPH), the 5-HT synthesizing enzyme (n = 21); of those cells, 86% were TPH immunoreactive, suggesting that the majority of recorded neurons was serotonergic. Calcium channel currents began to activate at about -40 mV in caudal raphe neurons and showed a peak amplitude of 952.2 +/- 144.2 (SE) pA at -10 mV. A small low-voltage activated current was also observed (approximately 22 pA). Calcium channel currents were potently inhibited by bath-applied 5-HT in most cells tested (approximately 90%). The EC50 for inhibition of calcium current by 5-HT was 0.1 microM; a saturating concentration (1.0 microM) blocked approximately 40% of the current evoked at 0 mV from a holding potential of -70 mV (n = 101). Current inhibition was associated with a slowing of activation kinetics and a shift in the peak of the current-voltage relationship, and was partially relieved by strong depolarizations. Current inhibition by 5-HT was mimicked by 8-OH-DPAT, a specific 5-HT1A agonist, and blocked by the 5-HT1a antagonists NAN 190 and (+) WAY 100135, but was unaffected by ketanserin, a 5-HT2A/C antagonist. omega-Conotoxin GVIA (omega-CgTx)-sensitive N-type channels and omega-agatoxin IVA (omega-AgaIVA)-sensitive P/Q-type channels together accounted for most of the calcium current (36 and 37%, respectively). Nimodipine had no effect on the calcium current, indicating that caudal raphe neurons do not express dihydropyridine-sensitive L-type currents. A substantial residual current (27%) remained after application of omega-CgTx, omega-AgaIVA, and nimodipine. Most of the 5-HT-sensitive calcium current was blocked by omega-CgTx and omega-AgaIVA; 5-HT had little effect on the residual current. Inhibition of calcium current by 5-HT was irreversible when GTP gamma S, a nonhydrolyzable guanosine 5'-triphosphate (GTP) analogue, was substituted for GTP in the pipette. In addition, the effects of 5-HT were blocked by pretreating slices with pertussis toxin (PTX). Together these data indicate that inhibition of N- and P/Q-type calcium current in serotonergic caudal raphe neurons is mediated by a 5-HT1A receptor via PTX-sensitive G proteins. Under current clamp, calcium channel toxins (omega-CgTx and omega-AgaIVA) and 5-HT each caused a decrease in the spike afterhyperpolarization and enhanced the repetitive firing response to injected current. The similar effects of 5-HT and the calcium channel toxins on firing behavior suggest that those effects of 5-HT were secondary to inhibition of N- and P/Q-type calcium channels.
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PMID:Effects of serotonin on caudal raphe neurons: inhibition of N- and P/Q-type calcium channels and the afterhyperpolarization. 908 3

Kava pyrones are the pharmacologically active compounds of Piper methysticum Forst. In the present study, the effect of the synthetic kava pyrone (+/-)-kavain was investigated on evoked contractile activity of isolated guinea-pig ileum. (+/-)-Kavain (1 microM-1 mM) dose-dependently reduced contractions of ileum evoked by carbachol (10 microM), by BAY K 8644 (0.3 microM), or by substance P (0.05 microM). (+/-)-Kavain also inhibited the contractile responses induced by raising the extracellular K+ concentration from 4 to 20 mM and by blocking the K+ channel by barium chloride (1 mM) or 4-aminopyridine (0.3 mM). After pre-incubation with 1 microM nifedipine, carbachol (1 microM) evoked 18.2 +/- 14.3% of contraction at control (i.e. prior pre-incubation with nifedipine). This remaining response was completely abolished by high concentrations of (+/-)-kavain (400 microM). After treatment of the longitudinal ileum strips with pertussis toxin (PTX), carbachol (1 microM) evoked 27.0 +/- 6.2% of the control response in untreated ileum. These contractions were also blocked by (+/-)-kavain (400 microM). However, (+/-)-kavain had no effect on the caffeine-induced (20 mM) contractions of ileum strips, which were permeabilized with digitonin or beta-escin. Moreover, it failed to affect Ca(2+)-evoked contractions of skinned muscles. These results suggest that the kava pyrone (+/-)-kavain may act in a non-specific musculotropic way on the smooth muscle membrane.
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PMID:Relaxation of evoked contractile activity of isolated guinea-pig ileum by (+/-)-kavain. 927 Mar 72


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