Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Current or voltage clamp recordings from CA3 neurones of the adult rat hippocampal slice were performed to study the inactivation properties of a slow outward K+ current identified as the delayed rectifier (IK). 2. In current clamp experiments, burst firing evoked from resting membrane potential by intracellular current injection was reduced or blocked by conditioning hyperpolarizing pre-pulses of 20-40 mV amplitude. This effect was inhibited by tetraethylammonium (TEA; 20 mM) but was unaffected by Cs+ (3 mM), 4-aminopyridine (4-AP; 2 mM), carbachol (30-50 microM), mast cell degranulating peptide (MCDP; 300 nM), thyrotrophin releasing hormone (TRH; 1 microM) or by a Ca(2+)-free solution containing Mn2+ or Co2+ (2 mM). 3. Single-electrode voltage clamp experiments were carried out on neurones superfused with Ca(2+)-free solution, containing tetrodotoxin (TTX; 1 microM), Mn2+ or Co2+ (2 mM), 4-AP (2 mM), Cs+ (3 mM) and carbachol (30 microM). Step depolarizations from a holding potential of -55 mV activated an outward current which reached a plateau after 200 ms, followed by an outward tail current. Such an outward current had the characteristics of IK. 4. The outward currents were significantly potentiated by conditioning hyperpolarizing pre-pulses suggesting the IK was reduced by a voltage-dependent inactivation process. Removal of inactivation was a function of the amplitude of the conditioning hyperpolarizing pre-pulse. At a holding potential of -55 mV removal of inactivation was time dependent with a time constant of 211 ms. High K+ (12.5 or 21.5 mM) solutions did not affect the inactivation characteristics of IK. 5. Tetraethylammonium (20 mM) or low concentrations of Ba2+ (0.1 mM) readily depressed the outward current without significantly affecting the inactivation process. Dendrotoxin (200 nM) also depressed such a slow current but, in addition, increased the inactivation process of IK. 6. It is suggested that removal of inactivation of IK by hyperpolarization can modulate cell excitability by fully restoring the ability of IK to inhibit burst firing of CA3 hippocampal neurones.
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PMID:Inactivation characteristics of a sustained, Ca(2+)-independent K+ current of rat hippocampal neurones in vitro. 133 65

4-Aminopyridine (4-AP), a known potassium channel blocker, was shown to induce histamine release from mast cells in mice. After ip 4-AP 5 mg.kg-1 the histamine content increased in blood, but decreased in the lung tissue. Calcium antagonists nifedipine (NIF) 500 mg.kg-1 ig, TMB-8 300 mumol.L-1 in vitro and potassium channel opener minoxidil (MIN) 100 mg.kg-1 inhibited the histamine release induced by 4-AP from mouse peritoneal mast cells (PMC). These results provide evidence that potassium channels are present in mouse mast cell membranes and indicate that the mechanism of histamine release by 4-AP may be related to the potassium channel blocking effect. As the result of this effect, the calcium channels open and the Ca2+ influx to the mast cells increases, thus eliciting histamine release.
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PMID:[4-Aminopyridine induced histamine release and its antagonism by certain drugs]. 752 60

1. Chinese hamster ovary cells (CHO), maintained in cell culture, were stably transfected with DNA for the MK-1 voltage-activated potassium channel, previously cloned from a mouse brain library. 2. Voltage-activated currents were recorded by the whole cell patch clamp method. In CHO cells transfected with the vector only, there were no significant outward voltage activated currents. However, large outward voltage-activated potassium currents were always observed in those cells which had been transfected with the vector containing the DNA encoding for MK-1. 3. These potassium currents activated from -40 mV, and reversed at the potassium equilibrium potential. The half-maximal conductance of MK-1 was at -10 mV and had a slope factor of 11 mV when fitted with a Boltzmann function. There was only very slight (< 10%) inactivation of MK-1 even at very large positive voltages. 4. MK-1 was reversibly blocked by: 4-aminopyridine (4-AP, 0.1-4 mM), Toxin I 10-100 nM), mast cell degranulating peptide (1 microM), tetraethylammonium (TEA, 4-10 mM), tedisamil (100 microM), quinine (100 microM) and ciclazindol (100 microM); all applied to the outside of the cell from a 'U tube' rapid perfusion system. 4-AP may block closed as well as open MK-1 potassium channels. 5. A synthetic 20 amino acid peptide derived from the N-terminus sequence of the Shaker B potassium channel (the 'inactivation peptide') produced dramatic inactivation of MK-1 when applied to the inside, but not the outside of the cell. Reducing peptide concentration or 'degrading' the peptide produced less inactivation. 6. The block of MK-1 by the synthetic inactivation peptide was quite different in time dependence from block by internal TEA (0.4-4 mM), which probably blocks much more quickly but less potently than the peptide.
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PMID:Pharmacology of a cloned potassium channel from mouse brain (MK-1) expressed in CHO cells: effects of blockers and an 'inactivation peptide'. 835 68

4-Aminopyridine (4-AP) was shown to promote histamine release from isolated rat peritoneal mast cells (PMC) in a dose-dependent manner. Potassium channel openers, minoxidil (Min) 200 mg.kg-1 ig, diazoxide (Dia) 500 mumol.L-1 in vitro and calcium antagonist nifedipine (Nif) 125 mg.kg-1 ig were found to inhibit 4-AP induced histamine release from rat PMC. Electron microscopy revealed that 4-AP caused partial degranulation of PMC and extrusion of granules and Min 200 mg.kg-1 ig retarded this phenomenon. These results provide evidence that potassium channels are present in rat mast cell membrane and indicate that the mechanism of histamine release by 4-AP may be related to its potassium channel blocking effect. As a result of this effect, the calcium channels open and Ca2+ influx to the mast cells increases, thus eliciting histamine release. Potassium channel openers seemed to be a new group of inhibitors of histamine release from mast cells.
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PMID:[Potassium channel openers antagonize 4-aminopyridine induced histamine release from rat peritoneal mast cells]. 870 28

1. The effects of potassium channel blocking compounds on synaptic transmission in the CA1 and dentate gyrus regions of the rat hippocampus were examined by means of simultaneous field potential recording techniques in brain slices. 2. 4-Aminopyridine (4-AP) enhanced the excitatory postsynaptic potential (e.p.s.p.) and induced multiple population spike responses in both regions. EC50 values were 6.7 microM in the CAI (n = 5) and 161.7 microM (n = 5) in the dentate gyrus. 3. Tetraethylammonium (TEA) increased the amplitude and induced broadening of the population spike in both regions. In the dentate gyrus (n = 5) a single slow spike response was introduced (EC50 12.8 mM) and in the CA1 region (n = 5) the response was transformed into two wide spikes (EC50 2.6 mM). 4. In the CA1 region all of the dendrotoxins (toxin I, toxin K, alpha-Dtx and delta-Dtx) induced multiple population spikes and enlarged e.p.s.p. responses. Potentials recorded simultaneously in the dentate gyrus exhibited comparatively minor enhancements. The EC50 value for toxin 1 in the CA1 was calculated to be 237 nM (n = 4). Estimated EC50 values were obtained for alpha-Dtx (1.1 microM, n = 3), toxin K (411 nM, n = 4) and delta-Dtx (176 nM, n = 3). 5. In the presence of toxin 1, DL-2-amino-5-phosphonovaleric acid (APV) induced slight reduction of the late e.p.s.p. phase (n = 3). 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) abolished all population spikes leaving a late slow positive waveform (n = 3). Co-application of APV and CNQX abolished all postsynaptic responses. 6. Charybdotoxin (CbTx) was significantly less potent than the dendrotoxins and had mixed actions in the CA1 region (n = 3). Again the dentate gyrus exhibited reduced sensitivity (n = 3). 7. In the presence of mast cell degranulating peptide (MCDP), enhancement of the CA1 field potential response (n = 5) was greater than that observed in the dentate gyrus (n = 5). 8. The results show that some potassium channel modulators can profoundly enhance CA1 region synaptic responses in the absence of notable changes in dentate gyrus excitability. Selective enhancement of defined synaptic pathways by potassium channel modulators may prove to have considerable therapeutic potential.
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PMID:The contrasting effects of dendrotoxins and other potassium channel blockers in the CA1 and dentate gyrus regions of rat hippocampal slices. 931 44

The antipruritic effects of the ethanol fractions of Humulus scandens on the 4-AP (4-aminopyridine)-induced and chloroquine-induced scratching in ICR mice were examined. The 40% ethanol fractions of H. scandens suppressed both the 4-AP- and chloroquine-induced scratching behavior, which significantly inhibited degranulation of rat peritoneal mast cell and antigen-stimulated histamine release. Further studies proved that the 40% ethanol fractions of H. scandens decreased the content of IL4 in serum of chloroquine-induced scratching ICR mice. The results suggest that the 40% ethanol fractions of H. scandens has antipruritic effects on both antihistamine-resistant and -sensitive pruritus.
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PMID:Antipruritic activity of extracts of Humulus scandens, the combinations of bioactive flavonoids. 2061 23