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)

The effects of dopamine (DA) on voltage-dependent Ca2+ currents were investigated in cultured rat lactotroph cells using the patch clamp recording technique. Each recorded cell was identified by the reverse hemolytic plaque assay. In the whole-cell configuration, two types of Ca2+ currents, L and T, were characterized on the basis of their kinetics, voltage sensitivity, and pharmacology. The L component had a threshold of -25 mV, showed little inactivation during a 150-msec voltage step, and was maximal at +10 mV. Cadmium ions (100 microM) significantly reduced its amplitude (75%). The T component was activated at a membrane potential close to -50 mV, was maximal at -10 mV, and showed a voltage-dependent inactivation between -90 and -30 mV. It was quickly inactivated during a maintained depolarization (time constant, 27 ms at -30 mV) and was strongly reduced (80%) by nickel ions (100 microM). Bath application of DA (10 nM) caused a markedly general depression of inward Ca2+ currents, acting differently on the T- and L-type currents. DA application shifted the voltage-dependence of the L-type current activation toward depolarization values (8 mV) without modifying its time- and voltage-dependent inactivation. In contrast, DA enhanced the inactivation of the T-type current by accelerating its time-dependent inactivation (25% decrease in the time constant of inactivation) and by shifting the voltage-dependence of the T-type current inactivation toward hyperpolarizing values (-63 mV in control vs. -77 mV in the presence of DA). These effects of DA were dose-dependent and involved the activation of a D2 receptor type. They were mimicked by bromocriptine application (10 nM), whereas sulpiride (100 nM) blocked the DA-evoked response. The D1 antagonist SCH 23390 was ineffective up to 100 microM. All of these DA-induced modifications in Ca2+ currents were abolished using a GTP-free pipette solution or after pretreatment of cells with pertussis toxin, suggesting that DA can regulate the function of Ca2+ channels through GTP-binding proteins (G-proteins). Our results show that DA acts simultaneously by reducing both voltage-dependent Ca2+ currents on lactotroph cells. Thus, DA reduces the entry of Ca2+ ions across the surface membrane and thereby influences electrical activity and the cytosolic free Ca2+ concentration involved in both basal and evoked PRL release.
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PMID:Dopamine inhibits two characterized voltage-dependent calcium currents in identified rat lactotroph cells. 216 20

We recently reported that dexamethasone (DEX) enhances acetylcholine (ACh) release from pituitary cell aggregates. In the present study, the effect of DEX on the GH-releasing properties of the cholinergic agonist carbachol (CCh) was investigated. Perifusion of hemipituitaries from 14-day-old rats with CCh stimulated basal GH release. CCh also increased basal GH release from organ-cultured pituitaries and from pituitary cells cultured as reaggregates, but only when the thyroid hormone T3 was supplemented to the culture medium. Pretreatment of the animals in vivo with DEX abolished the CCh-induced increase in basal GH release from hemipituitaries tested in vitro. Treatment of pituitary organ cultures and reaggregate cell cultures with DEX reversed the stimulation of basal GH release by CCh into an inhibition. CCh also inhibited isoproterenol- and GRF-stimulated GH release from DEX-treated pituitary cell reaggregates. In contrast, the responsiveness of tumoral GH3 cell aggregates to CCh was not dependent on T3 or DEX during culture. The half-maximal concentration of CCh for inhibition was significantly lower than that for stimulation (1 and 10 microM, respectively). Perifusion with CCh of DEX-treated cell reaggregates consisting of a highly enriched somatotroph population (greater than 90% GH immunoreactive cells), obtained by sequential velocity and buoyant density sedimentation of dispersed cells, also inhibited basal GH release. Pretreatment of pituitary cell reaggregates cultured in DEX-supplemented medium with pertussis toxin completely abolished the inhibition by CCh. The inhibition of GH release by CCh was not affected by the Na+ conductance blocker tetrodotoxin, the Cl- channel blocker picrotoxin, or the K+ channel blocker caesium, but was abolished by the Ca2+ channel blockers cadmium and verapamil. In conclusion, CCh is capable of both stimulating and inhibiting GH release in different pituitary in vitro assay systems; the inhibition is dependent on glucocorticoids and the stimulation on the thyroid hormone T3. The mechanism of action of the inhibition seems to involve a GTP-binding protein and most probably a decrease in calcium conductance in the somatotroph.
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PMID:The glucocorticoid hormone dexamethasone reverses the growth hormone-releasing properties of the cholinomimetic carbachol. 270 69

The influence of calcium channel antagonists, felodipine and cadmium, as well as pertussis toxin on noradrenaline-induced contractions in pulmonary artery rings from rats with pulmonary hypertension induced by monocrotaline (MCT) were examined. MCT-treated rats had pulmonary hypertension, right ventricular hypertrophy and lung oedema, as compared to corresponding vehicle-treated rats. The MCT-treated animals did not have polycythemia as compared to vehicle-treated rats. Pre-treatment of pulmonary artery rings from MCT-treated rats with felodipine and cadmium significantly reduced the maximum response without altering the EC50 or the Hill coefficient of concentration-response curve to noradrenaline. In pulmonary artery rings from vehicle-treated rats, felodipine significantly increased the EC50 and reduced the maximum response and the Hill coefficient of the concentration-response curve to noradrenaline. In contrast, cadmium did not alter these parameters in pulmonary artery rings from vehicle-treated rats. Pertussis toxin did not affect noradrenaline-induced contractions in pulmonary artery rings from vehicle- or MCT-treated rats. Felodipine, cadmium and pertussis toxin were ineffective in inhibiting noradrenaline-induced contractions in aortic rings from either vehicle- or MCT-treated rats. Our results can be interpreted to indicate that alteration to voltage operated, felodipine-sensitive, calcium channels as well as, cadmium-sensitive sites contribute to the changes observed in the functional behavior of pulmonary blood vessels from pulmonary hypertensive rats.
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PMID:Effects of calcium channel antagonists and pertussis toxin on noradrenaline-induced contractions in pulmonary artery from pulmonary hypertensive rats. 747 94

Thapsigargin elicits histamine release on rat mast cells, and this effect is increased if cells are pretreated with thapsigargin before the addition of external calcium. Okadaic acid does not modify the response of mast cells to thapsigargin, while sodium fluoride or the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) increases several fold the sensitivity of cells to thapsigargin. On the other hand, pertussis and cholera toxins inhibit the response to thapsigargin. Thapsigargin increases the activity of the Na(+)-H+ exchanger, this effect being blocked by fluoride and not modified by TPA. The metals cadmium and lanthanum completely block the effect of TPA or thapsigargin on the Na(+)-H+ exchanger. The influx of 45Ca in rat mast cells is not modified by thapsigargin, but if cells are treated with thapsigargin before the addition of calcium, the influx is markedly increased in the first 2 min before returning to normal. Our results indicate that exocytosis is modulated by crosstalks between intracellular calcium, cytosolic pH and external calcium.
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PMID:Effect of signal transduction pathways on the action of thapsigargin on rat mast cells. Crosstalks between cellular signalling and cytosolic pH. 751 22

The effect of (R,S)-(3,4-dihydro 6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl- N,N-di-[2-(2,3,4-trimethoxyphenyl)ethyl]-acetamide (LOE 908), a cation channel blocker in HL-60 promyeloblasts, was studied in the A7r5 smooth muscle cell line from rat thoracic aorta, using the whole-cell patch-clamp technique. At a holding potential of -60 mV, application of vasopressin induced a nonselective cation conductance in voltage-clamped A7r5 cells. The current-voltage relation was linear, and currents reversed close to 0 mV regardless of the chloride gradient. The activation of the nonselective cation conductance by vasopressin was not affected by dialysing cells with Ca(2+)-free internal solution. LOE 908 blocked this current in a concentration-dependent manner with an IC50 of 560 nM, whereas dihydropyridine-sensitive Ba2+ current through voltage-dependent Ca2+ channels was blocked with an IC50 of 28 microM. Another organic blocker of receptor-mediated Ca2+ entry, 1-beta-[3-(4-methoxyphenyl)-propoxy]-4-methoxyphenethyl-1H-imidazole hydrochloride (SK&F 96365), blocked both, the vasopressin-induced nonselective conductance and the voltage-activated Ba2+ current with similar IC50 values of 13 microM and 8 microM, respectively. The rank order of potency of inorganic blockers on the vasopressin-induced inward current was Gd3+ > La3+ > Cd2+. Vasopressin-induced non-selective cation current was also observed in pertussis toxin-pretreated A7r5 cells but was completely abolished after infusion of the GDP analogue, guanosine 5'-O-[3-thio]diphosphate, from the patch pipette. Furthermore, vasopressin induced a transient outward current, suggesting a Ca(2+)-activated K(+)-current, which overlapped with the nonselective cation conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The isoquinoline derivative LOE 908 selectively blocks vasopressin-activated nonselective cation currents in A7r5 aortic smooth muscle cells. 751 40

We investigated whether maitotoxin activates non-selective cation channels, as was recently proposed [Soergel, Yasumoto, Daly and Gusovsky (1992) Mol. Pharmacol. 41, 487-493]. Stimulation of dibutyryl cyclic AMP-differentiated HL-60 cells with the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP; 0.1 microM), the Ca(2+)-ATPase inhibitor thapsigargin (0.1 microM) or maitotoxin (25 ng/ml) resulted in an increase in cytoplasmic free calcium concentration ([Ca2+]i). Unlike fMLP and thapsigargin, maitotoxin produced no increase in [Ca2+]i in the absence of extracellular Ca2+. The increase in [Ca2+]i induced by fMLP was blocked by pretreatment with pertussis toxin (100 ng/ml for 24 h) but not that induced by maitotoxin. Similarly, the increase in [Ca2+]i produced by fMLP but not that produced by maitotoxin was inhibited by pretreatment with phorbol myristate acetate (100 ng/ml). Both fMLP- and maitotoxin-induced increases in [Ca2+]i were blocked by 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenylethyl)-1H-imid azole hydrochloride (SKF 96365) in a concentration-dependent manner. However, the maitotoxin-induced increase in [Ca2+]i was more sensitive to inhibition by SKF 96365 than the fMLP-induced increase. fMLP-induced increases in [Ca2+]i were blocked by cations with Gd3+ being more effective than Cd2+, whereas for maitotoxin Cd2+ was more effective than Gd3+. Both fMLP and thapsigargin stimulated quenching of Fura-2 fluorescence in the presence of extracellular Mn2+, whereas maitotoxin produced no Mn2+ quenching. Taken together these results suggest that maitotoxin does not stimulate the nonselective cation channel activated by fMLP, but instead activates Ca2+ influx by a different mechanism.
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PMID:Maitotoxin activates cation channels distinct from the receptor-activated non-selective cation channels of HL-60 cells. 751 11

Variations in intracellular free calcium concentration (delta[Ca2+]i) were measured in intact and isolated human astrocytoma cells (U373 MG) loaded with fura-2 acetoxymethylester. Microperfusion of 50 nM substance P (SP), applied for 1 s, increased [Ca2+]i by 351 nM from a stable basal level of [Ca2+]i of 26 nM. The peak delta[Ca2+]i induced by SP was dose dependent with a threshold of 10(-3) nM, an ED50 of 1.3 nM and a maximal effect for concentrations of SP greater than 100 nM. The NK1 receptor agonist, [Sar9Met(O2)11]SP, mimicked the effect of SP, while the NK2 and NK3 selective receptor agonists, [N1(10)]NKA(4-10) and senktide, respectively, had no effect. The delta[Ca2+]i induced by SP was unaffected by 100 microM cadmium or by removal of extracellular calcium ions. Caffeine up to 30 mM had no effect on [Ca2+]i. In contrast, thapsigargin increased resting [Ca2+]i by 92 nM and reduced the delta[Ca2+]i induced by SP. A pertussis treatment (500 ng/ml-24 h) did not modify the delta[Ca2+]i induced by SP. We conclude that SP, acting on a NK1 receptor, mobilizes cytosolic calcium from an intracellular calcium pool which can be partially depleted by thapsigargin.
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PMID:Mobilization of intracellular calcium by substance P in a human astrocytoma cell line (U-373 MG). 752 79

The increase in intracellular free Ca2+ ([Ca2+]i) associated with interaction of monocyte chemotactic protein-1 (MCP-1) and related chemokines beta with adherent human blood monocytes was investigated at the single-cell level. We used f-MLP as reference chemotactic agent. MCP-1 caused an increase in [Ca2+]i in individual adherent monocytes, with 95% of cells responding to the chemokine at 20 ng/mL. Response to MCP-1 was already detectable at 1 pg/mL, whereas at least 5 ng/mL were required for significant chemotactic response. The kinetics of the increase in [Ca2+]i were considerably different for MCP-1 compared with f-MLP. MCP-1 produced a slow increase of [Ca2+]i that reached a plateau in 5 to 7 minutes. On the other hand, the increase of [Ca2+]i induced by f-MLP appeared to be biphasic, with a fast phase peaking after 5 to 40 seconds followed by a slower wave. Blocking of Ca2+ channels by Ni2+ or Cd2+ and/or chelation of extracellular free Ca2+ considerably reduced but did not abolish response to MCP-1, had no effect on the first wave of [Ca2+]i induced by f-MLP, and completely abrogated the second, slower wave. Thapsigargin, which empties intracellular Ca2+ stores, inhibited f-MLP-induced [Ca2+]i increase but fully blocked the action of MCP-1 only when combined with Ni2+. Thus, increase of [Ca2+]i induced by MCP-1 is apparently due to independent opening of a channel and mobilization from intracellular stores, whereas f-MLP-induced mobilization of Ca2+ from stores causes subsequent opening of a channel. At variance with MCP-1, the related chemokine MCP-2 induced only a low increase of [Ca2+]i in about 40% of adherent monocytes. Inhibition of chemokine-induced increase of [Ca2+]i by cholera or pertussis toxin indicated that MCP-1 and MCP-2 activate monocytes through different intracellular pathways. These results demonstrate at the single-cell level that the mechanisms and dynamics of increased [Ca2+]i are considerably different for f-MLP and chemokines beta. In addition, the [Ca2+]i increase induced by the two related chemokines beta MCP-1 and MCP-2 appears to be differently regulated, suggesting interaction with distinct receptors.
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PMID:Single-cell analysis of macrophage chemotactic protein-1-regulated cytosolic Ca2+ increase in human adherent monocytes. 766 86

1. Intracellular recordings were made from submucosal neurones and single-electrode voltage-clamp methods were used to record membrane currents. The actions of substance P (SP), 5-hydroxytryptamine (5-HT), muscarine, vasoactive intestinal polypeptide (VIP), forskolin and nerve stimulation were studied. 2. Substance P, 5-HT (in the presence of 5-HT3 receptor antagonists), muscarine, VIP, forskolin and slow excitatory synaptic transmission all produced identical responses: an inward current associated with a membrane conductance decrease at the resting potential. The actions of any one occluded the actions of any other and all responses were pertussis-toxin insensitive. 3. These agonists produced a voltage-independent decrease in a 'leak' potassium conductance between -40 and -120 mV in 14% of neurones. 4. These agonists decreased a voltage-dependent, calcium-activated potassium conductance between -40 and -80 mV in all other (86%) neurones. The agonists still evoked an inward current without apparent conductance change at potentials between -90 and -130 mV. 5. In a low calcium solution containing cobalt or cadmium, the agonists produced an inward current associated with a conductance increase from -40 to -120 mV. Ion replacement studies indicated this current was due to an increase in a cation-selective (mainly sodium) conductance. 6. The agonists also reduced the inwardly rectifying potassium current that is activated by somatostatin and alpha 2-adrenoceptor agonists in these neurones. The agonists did not alter the inwardly rectifying potassium current that is present in these neurones in the absence of somatostatin or alpha 2-agonists. 7. Thus, SP, 5-HT, muscarine, VIP and the release of slow excitatory transmitters all appear to act through a common intracellular transduction pathway, an increase in adenylate cyclase. This results in an activation of a sodium-selective cation current and an inhibition of three distinct potassium conductances: the background potassium conductance, the calcium-activated potassium conductance and the inwardly rectifying potassium conductance activated by somatostatin and alpha 2-adrenoceptor agonists.
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PMID:Common ionic mechanisms of excitation by substance P and other transmitters in guinea-pig submucosal neurones. 768 94

1. Regulation of membrane potential by extracellular Ca2+ concentration ([Ca2+]o) was examined in freshly isolated rabbit osteoclasts. 2. The resting membrane potential of osteoclasts was close to the K+ equilibrium potential in 1 mM Ca2+ medium. An elevation of [Ca2+]o caused membrane depolarization, accompanied by a decrease in the membrane conductance. 3. The inwardly rectifying K+ current observed under voltage clamp was dose-dependently inhibited by an elevation of [Ca2+]o, which explained the membrane depolarization caused by high [Ca2+]o. 4. Other divalent cations also inhibited the inwardly rectifying K+ current with the following order of potency: Ca2+ < Ni2+ < or = Co2+ < Cd2+. 5. In the presence of intracellular GTP gamma S the inwardly rectifying K+ current was irreversibly inhibited by [Ca2+]o, whereas the inhibition of the inwardly rectifying K+ current was greatly attenuated by intracellular application of GDP beta S. 6. Pertussis toxin (PTX) treatment did not abolish the inhibition of the inwardly rectifying K+ current caused by [Ca2+]o. 7. These results suggest that inwardly rectifying K+ channels in osteoclasts were regulated by a PTX-insensitive G-protein, which was coupled to the putative Ca2+ receptor or sensor on the cell membrane.
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PMID:Inhibition of inwardly rectifying K+ current by external Ca2+ ions in freshly isolated rabbit osteoclasts. 786 41


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