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

The ability of cations to modulate the binding of the sigma 1 receptor-selective ligand (+)-[3H]pentazocine to guinea pig cerebellum was investigated. Di- and trivalent cations biphasically inhibited (+)-[3H]pentazocine binding, revealing multiple affinity states. The rank order of potency of these cations (based on the high affinity component of inhibition) was Zn2+ > Co2+ >> La3+ = Ni2+ = Cd2+ = Mn2+ = Gd2+ > Ba2+ = Sr2+ >> Mg2+ > Ca2+. The inhibition of 1,3-[3H]di(2-tolyl)guanidine binding to the sigma 2 receptor by these cations differed qualitatively and quantitatively from their effects on (+)-[3H]pentazocine binding. Although monovalent cations decreased the Kd for (+)-[3H]pentazocine binding, divalent cations split (+)-[3H]pentazocine binding into low and high affinity components. The Bmax of the high affinity component decreased with increasing divalent cation concentrations. Both mono- and divalent cations significantly reduced the rate of association of (+)-[3H]pentazocine with the sigma 1 receptor without altering the dissociation rate. (+)-[3H]Pentazocine binding was not altered by guanine nucleotides or by treatment with cholera or pertussis toxins. However, nonselective cation channel blockers (cinnarizine, hydroxyzine, prenylamine, amiodarone, and proadifen) potently inhibited (+)-[3H]pentazocine binding. These results indicate that physiologically relevant concentrations of divalent cations allosterically modulate (+)-[3H]pentazocine binding to the sigma 1 receptor, to reveal multiple affinity states. These sites do not represent sigma 1 to sigma 2 subtype interconversion or ternary complex formation with guanine nucleotide-binding proteins. However, the rank order of cation potency and the inhibition of binding by cation channel blockers is consistent with a potential role for sigma receptors as constituents of cation channels.
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PMID:Modulation of (+)-[3H]pentazocine binding to guinea pig cerebellum by divalent cations. 127 78

Because increasing evidence indicates that glial cells are a target of endothelin, we have characterized endothelin-induced phosphoinositide (PI) turnover and Ca2+ homeostasis in C6 glioma cells. Endothelin-1 (ET) increased formation of 3H-inositol phosphate (IP) from PI and elicited an increase in cytosolic free Ca2+ ([Ca2+]i) in rat C6 glioma. In the presence of Li+, the increase in 3H-inositol trisphosphate formation was rapid, reaching its peak at 5 min after stimulation. ET also elicited a rapid and sustained increase in [Ca2+]i in a dose-dependent manner (1-100 nM). The rank orders of efficacy for ET-related peptides in increasing [Ca2+]i were ET = ET-2 greater than sarafotoxin greater than ET-3. Both ET-mediated stimulation of IP formation and [Ca2+]i increase were largely inhibited in the absence of external Ca2+ but unaffected by the depletion of external Na+ and the presence of dihydropyridine derivatives or verapamil. Inorganic Ca2+ channel blockers Cd2+, La3+, and Mn2+ at 1 mM inhibited both responses induced by ET. Cross-desensitization and nonadditivity were observed for both events among ET-related peptides tested, but not between ET and ATP. Pretreatment of cells with pertussis toxin (PTX) attenuated the PI response to ET, but had no effect on ET-elicited [Ca2+]i increase. ET-induced Ca2+ mobilization (measured in Ca(2+)-free medium) was only transient and was inhibited by 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate. Moreover, the intracellular Ca2+ pools mobilized by ET and ATP appeared to overlap, as indicated by their partial heterologous desensitization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological characterization of endothelin-stimulated phosphoinositide breakdown and cytosolic free Ca2+ rise in rat C6 glioma cells. 131 33

1. The effects of bradykinin on nociceptors have been characterized on a preparation of the neonatal rat spinal cord with functionally connected tail maintained in vitro. Administration of bradykinin to the tail activated capsaicin-sensitive peripheral fibres and evoked a concentration-dependent (EC50 = 130 nM) depolarization recorded from a spinal ventral root (L3-L5). 2. The response to bradykinin was unaffected by the peptidase inhibitors, bestatin (0.4 mM), thiorphan (1 microM), phosphoramidon (1 microM) and MERGETPA (10 microM) or by the presence of calcium blocking agents, cadmium (200 microM) and nifedipine (10 microM). 3. Inhibition of cyclo-oxygenase with indomethacin (1-5 microM), aspirin (1-10 microM) and paracetamol (10-50 microM) consistently attenuated responses to bradykinin. 4. The effect of bradykinin was mimicked by the phorbol ester PDBu, an activator of protein kinase C. The response to bradykinin was attenuated following desensitization to PDBu but desensitization to bradykinin did not induce a cross-desensitization to PDBu. The protein kinase C inhibitor staurosporine (10-500 nM) consistently attenuated the effects of PDBu and bradykinin. 5. Bradykinin responses were reversibly enhanced by dibutyryl cyclic AMP (100 microM). However dibutyryl cyclic GMP (0.5 mM) and nitroprusside (10 microM) produced prolonged block of responsiveness to bradykinin. Prolonged superfusion with pertussis toxin did not affect responses to bradykinin. 6. The B1-receptor agonist des Arg9-bradykinin (10-100 microM) was ineffective alone or after prolonged exposure of the tail to lipopolysaccharide (100 ng ml-1) or epidermal growth factor (100 ng ml-1) to induce B1 receptors. The BI-receptor antagonist, des Arg9 Leu8-bradykinin (10 JM) did not attenuate the response to bradykinin. A number of bradykinin B2 antagonists selectively and reversibly attenuated the response to bradykinin. The rank order potency was Hoe 140> LysLys [Hyp3,Thi5 8,D-Phe7]-bradykinin> D-Arg[Hyp3, Thi5'8, D-Phe7]-bradykinin = D-Arg[Hyp2,Thi5'8, D-Phe7]-bradykinin.7. These data show that bradykinin produces concentration-dependent activation of peripheral nociceptors in the neonatal rat tail. The responses were unaffected by calcium channel block and were partially dependent on the production of prostanoids. Bradykinin-evoked responses were consistent with the activation of protein kinase C-dependent mechanisms. Cyclic GMP-dependent mechanisms may be involved in bradykinin-receptor desensitization whereas cyclic-AMP dependent mechanisms increase fibre excitability and facilitate bradykinin-induced responses. The effects of bradykinin were mediated by a B2 receptor.
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PMID:Bradykinin-induced activation of nociceptors: receptor and mechanistic studies on the neonatal rat spinal cord-tail preparation in vitro. 133 51

1. We have examined the effects of neuropeptide Y (NPY) on synaptic transmission and [Ca2+]i signals in rat hippocampal neurones grown in culture. [Ca2+]i in individual neurones displayed frequent spontaneous fluctuations often resulting in an elevated plateau [Ca2+]i. These fluctuations were reduced by tetrodotoxin (1 microM) or combinations of the excitatory amino acid antagonists 6-cyano-7-dinitro-quinoxaline (CNQX) (10 microM) and aminophosphonovalerate (APV) (50 microM), indicating that they were the result of glutamatergic transmission occurring between hippocampal neurones. 2. [Ca2+]i fluctuations were also prevented by Ni2+ (200 microM), by the GABAB receptor agonist, baclofen (10 microM) and by NPY (100 nM) or Y2 receptor-selective NPY agonists. Following treatment of cells with pertussis toxin, NPY produced only a brief decrease in [Ca2+]i fluctuations which rapidly recovered. 3. Perfusion of hippocampal neurones with 50 mM K+ produced a large rapid increase in [Ca2+]i. This increase was slightly reduced by NPY or by a combination of CNQX and APV. The effects of CNQX/APV occluded those of NPY. NPY had no effect on Ba2+ currents measured in hippocampal neurones under whole cell voltage-clamp even in the presence of intracellular GTP-gamma-S. On the other hand, Ba2+ currents were reduced by both Cd2+ (200 microM) and baclofen (10 microM). 4. Current clamp recordings from hippocampal neurones demonstrated the occurrence of spontaneous e.p.s.ps and action potential firing which were accompanied by increases in [Ca2+]i. This spontaneous activity and the accompanying [Ca2+]i signals were prevented by application of NPY (100 nM). When hippocampal neurones were induced to fire trains of action potentials in the absence of synaptic transmission, these were accompanied by an increase in cell soma [Ca2+]j. NPY (100 nM) had no effect on these cell soma [Ca2+], signals. NPY (100 nM) also had no effect on inward currents generated in hippocampal neurones by micropipette application of glutamate (50 microM).5. Thus, NPY is able to abolish excitatory neurotransmission in hippocampal cultures through a pertussis toxin-sensitive mechanism. However, no effect of NPY on Ca2+ influx into the cell soma of these hippocampal neurones could be discerned. These results are consistent with a localized presynaptic inhibitory effect of NPY on glutamate release in hippocampal neurones in culture.
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PMID:Investigations into neuropeptide Y-mediated presynaptic inhibition in cultured hippocampal neurones of the rat. 135 89

This study characterized cytosolic free Ca2+ concentration ([Ca2+]i) in normal and thermally injured human epidermoid A 431 cells. The resting [Ca2+]i in normal cells at 37 degrees C was 87 +/- 5 nM (n = 105). When cells were subjected to hyperthermia (40-50 degrees C), [Ca2+]i increased in a temperature- and time-dependent manner. The maximal increase in cells exposed to 45 degrees C was observed at 20 min; [Ca2+]i returned to normal within 1 h. The heat-induced [Ca2+]i increase depended on the presence of external Ca2+. La3+ and Cd2+ but not Co2+, verapamil, or nifedipine attenuated the heat-induced [Ca2+]i increase. TMB-8 partially blocked the increase in [Ca2+]i but pertussis toxin and cholera toxin pretreatment did not. The magnitude of the heat-induced [Ca2+]i increase or 45Ca2+ uptake depended on the presence of extracellular Na+. Heat treatment reduced the apparent Michaelis constant for external Ca2+ from 490 +/- 91 to 210 +/- 60 microM, whereas the maximal velocity remained the same. The intracellular Na+ concentration decreased 62.5% after heating. The heat-induced [Ca2+]i increase was completely blocked by amiloride (5 microM) and 5'-(N,N-dimethyl)-amiloride (1 microM). These results suggest heat activates the Na(+)-Ca2+ exchange system so as to increase [Ca2+]i and reduce [Na+]i.
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PMID:Heat shock increases cytosolic free Ca2+ concentration via Na(+)-Ca2+ exchange in human epidermoid A 431 cells. 163 82

1. Intracellular and whole-cell recordings were made from primary cultures of rat intermediate pituitary cells; beta-endorphin secretion was also measured by radioimmunoassay. The effects of dopamine receptor activation on hormone secretion, calcium currents and resting potassium conductance were compared. 2. Spontaneous sodium-dependent action potentials occurred in 82% of cells recorded with intracellular microelectrodes and 64% of cells recorded with whole-cell patch electrodes; the same proportion of cells showed spontaneous calcium-dependent depolarizations in the presence of tetrodotoxin. 3. Calcium currents recorded from holding potentials of -90 or -70 mV showed transient and sustained components, both of which activated at -40 mV and had similar current-voltage relations. Bay K 8644 (1 microM) increased both components by about 130% while nifedipine (1-10 microM) decreased them by a maximum of 30%. Nickel (500 microM) inhibited transient and sustained components by 68 and 50%; cadmium (100 microM) abolished the current. omega-Conotoxin (1 microM) reversibly inhibited the transient component by 26%. 4. The dopamine D2 receptor agonist, quinpirole (0.1-10 microM) inhibited transient and sustained components in all cells by a maximum of 40 and 25% respectively. Quinpirole did not alter the time course of the current. 5. Quinpirole (1-100 nM) hyperpolarized 90% of cells from which intracellular recordings were made and 55% of cells recorded from with whole-cell patch pipettes. Maximum hyperpolarization of 16 +/- 4 mV from a resting potential of -44 +/- 5 mV was observed with 100 nM-quinpirole; concentration producing half-maximal effect was 3 nM. The hyperpolarization resulted from an increase in potassium conductance. 6. Quinpirole (1-100 nM) decreased basal beta-endorphin secretion by 55% and abolished secretion stimulated by Bay K 8644 or isoprenaline; concentrations producing half-maximal inhibitions were 5-10 nM. Tetrodotoxin (1 microM), nifedipine (1 microM), nickel (500 microM) and cadmium (100 microM) did not alter basal or stimulated secretion although higher concentrations of cadmium did inhibit stimulated hormone release. 7. Pertussis toxin pre-treatment prevented all actions of quinpirole. 8. Thus, concentrations of quinpirole that abolished stimulated hormone secretion did not alter calcium currents; conversely, concentrations of calcium channel blockers that partially or completely inhibited calcium currents did not alter basal or stimulated secretion. These results may indicate that calcium influx through the voltage-dependent calcium channels measured in these experiments does not contribute significantly to hormone release from melanotrophs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dopamine actions on calcium currents, potassium currents and hormone release in rat melanotrophs. 171 75

Endothelin (ET)-related peptides robustly stimulated [3H]-inositol phosphate (IP) formation in cultured cerebellar granule cells, astrocytes, and C6 glioma cells. Their agonist selectivities were ET-1 = ET-2 greater than or equal to sarafotoxin S6b greater than ET-3 greater than big ET-1 for granule cells and ET-1 greater than or equal to ET-2 greater than or equal to S6b greater than big ET-1 greater than ET-3 for cerebellar astrocytes and C6 glioma cells. These effects were Ca(2+)-dependent but insensitive to antagonists of L-type Ca2+ channels and the Na+/Ca2+ antiporter. Pretreatment of cells with ET-1 or S6b induced homologous desensitization of phosphoinositide (PI) response mediated by ET receptors. Long-term pertussis toxin (PTX) treatment attenuated the phosphoinositide (PI) response in astrocytes and glioma but not in granule cells. ET-1 and its related peptides increased [Ca2+]i in C6 glioma by two distinct pathways: IP3-induced Ca2+ mobilization or receptor-operated Ca2+ influx. La3+, Mn2+, and Cd2+ inhibited the Ca2+ influx and sustained PI turnover, while Ca2+ mobilization was attenuated by phorbol ester and TMB-8. ET-induced Ca2+ influx was essential for the sustained [Ca2+]i increase and PI turnover. Homologous desensitization of [Ca2+]i increase was also noted. In cerebellar granule cells, ET evoked the release of [3H]D-aspartate from these neurons. This action appears to be dependent on PI hydrolysis and [Ca2+]i increase and modulated by protein kinase C.
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PMID:Endothelin-induced activation of phosphoinositide turnover, calcium mobilization, and transmitter release in cultured neurons and neurally related cell types. 172 40

1. Somatotrophs were obtained from rat pituitary glands after dissociation, separation and enrichment on a continuous gradient of bovine serum albumin at unit gravity. Somatotrophs were enriched up to 85% in the heavy fractions (F8 and F9). 2. After identification by reverse hemolytic plaque assay, patch-clamp recording in the whole-cell mode was performed on somatotrophs. 3. Under voltage-clamp conditions, two types of Ca2+ currents were recorded. From a holding potential of -70 mV, depolarizing voltage steps to potentials more positive than -50 mV activated a current which rapidly inactivated and which was very sensitive to Ni2+ but not to Cd2+. This current corresponds to T-type current. Depolarizing steps to potentials more positive than -30 mV from a holding potential of -40 mV triggered a current which slowly inactivated and which was very sensitive to Cd2+ but not to Ni2+. This current corresponds to L-type current. 4. Application of somatostatin to the bath solution (10 nM) markedly reduced the amplitudes of both T- and L-type currents. Somatostatin decreased the conductance of L-type current without modifying its time- and voltage-dependent inactivation but its activation was not affected. However, somatostatin decreased the conductance of T-type currents, and also accelerated its time-dependent inactivation. Half-inactivation voltage of T-type current was shifted from -52 to -63 mV by somatostatin but no change was obtained in the current activation curve. 5. All these modifications in Ca2+ currents were abolished by a pre-treatment of the cultures with pertussis toxin (100 ng/ml, for 10 h). This pre-treatment also blocked the inhibitory effect of somatostatin on high-K(+)-stimulated growth hormone release. 6. Our results show that somatostatin acts on somatotrophs by attenuating the voltage-dependent Ca2+ currents. These effects may contribute to a somatostatin-induced reduction in [Ca2+]i and the subsequent decline in growth hormone release.
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PMID:Two types of voltage-dependent calcium current in rat somatotrophs are reduced by somatostatin. 197 2

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


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