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A Den Hertog

Publications and source records attributed to A Den Hertog.

At least 19 recordsLinked to original sources
PubMed1996

Plasma membrane Ca2+ pumping plays a prominent role in adenosine A1 receptor mediated changes in [Ca2+]i in DDT1 MF-2 cells.

Adenosine A1 receptor mediated formation of inosito 1,4,5-trisphosphate (Ins(1,4,5)P3) and accumulation of cytoplasmic Ca2+ ([Ca2+]i) were investigated in DDT1 MF-2 smooth muscle cells. A strong reduction of the adenosine and N6-cyclopentyladenosine (CPA) induced rise in [Ca2+]i was observed after blocking Ca2+ entry across the plasma membrane with LaCl3. This effect of LaCl3 was not observed in the absence of extracellular Ca2+; it was not caused by reduced Ins(1,4,5)P3 formation or changed Ins(1,4,5)P3 induced Ca2+ release, or influenced by temperature. The inhibition of the CPA induced increase in [Ca2+]i by LaCl3 was strongly counteracted in the presence of ortho-vanadate, an inhibitor of plasma membrane Ca2+ ATPase. Ortho-vanadate might also reduce protein tyrosine-phosphate phosphatase activity involved in tyrosine kinase mediated phospholipase C (PLC) activation. However, ortho-vanadate and tyrphostin 25, a tyrosine kinase inhibitor, did not affect the CPA induced formation of Ins(1,4,5)P3. Taken together, these results show a strong contribution of Ca2+ pumping across the plasma membrane to the regulation of [Ca2+]i mediated by adenosine A1 receptors. Na+/Ca2+ exchange only played a minor role in the initial phase of CPA induced Ca2+ metabolism as measured in low Na+ containing solution. The mechanism by which adenosine A1 receptors activate plasma membrane Ca2+ ATPase pumps does not include direct stimulation of pumps, but most likely involves an indirect pathway activated by a rapid increase in [Ca2+]i.

Adenosine↗
PubMed1996

Neomycin inhibits histamine and thapsigargin mediated Ca2+ entry in DDT1 MF-2 cells independent of phospholipase C activation.

The histamine H1 receptor mediated increase in cytoplasmic Ca2+ ([Ca2+]i) was measured in the presence of the known phospholipase C (PLC) inhibitor, neomycin. Neomycin (1 mM) inhibited the histamine (100 microM) induced rise in [Ca2+]i to the same extent as observed after blocking Ca2+ entry with LaCl3. Likewise, the increase in [Ca2+]i after re-addition of CaCl2 (2 mM) to extracellular Ca2+ deprived and histamine pretreated cells was strongly reduced by neomycin. However, neomycin did not inhibit the histamine induced formation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) or the release of Ca2+ from internal stores. These results show that neomycin blocks histamine induced Ca2+ entry independent of phospholipase C activation. Inhibition of intracellular store Ca(2+)-ATPase by thapsigargin (1 microM), elicited an increase in [Ca2+]i due to a leakage from the stores, subsequently followed by store-dependent Ca2+ entry. Thapsigargin induced Ca2+ entry was also completely blocked by neomycin. These results indicate that neomycin inhibits histamine and thapsigargin induced Ca2+ entry. This inhibition is most likely exerted at the level of plasma membrane Ca2+ channels.

Animals↗
PubMed1995

The role of inositol 1,3,4,5-tetrakisphosphate in internal Ca2+ mobilization following histamine H1 receptor stimulation in DDT1 MF-2 cells.

Receptor-activated formation of inositol phosphates results in mobilization of intracellular stored Ca2+ in a variety of cells, including vas deferens derived DDT1 MF-2 cells. Stimulation of the histamine H1 receptor on these cells caused a pronounced formation of inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) with respect to that of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3). In this study, the role of inositol phosphates, in particular Ins(1,3,4,5)P4 on the internal Ca(2+)-releasing process was investigated in permeabilized and histamine-stimulated intact DDT1 MF-2 cells. In permeabilized cells. Ins(1,4,5)P3 induced a concentration-dependent release of intracellular stored Ca2+. Addition of Ins(1,3,4,5)P4 did not cause Ca2+ mobilization, but its presence enhanced the amount of Ca2+ released by Ins(1,4,5)P3, thereby increasing the total Ca(2+)-releasing capacity. The effect of both inositol phosphates was inhibited by heparin, known to block Ins(1,4,5)P3-sensitive receptors. Thus, the additional amount of Ca2+ released by Ins(1,3,4,5)P4 is mediated, either via Ins(1,4,5)P3-sensitive Ca2+ channels, or via different heparin-sensitive Ca2+ channels activated by both Ins(1,4,5)P3 and Ins(1,3,4,5)P4. Histamine H1 receptor stimulation in intact cells induced a Ca(2+)-dependent K+ current, representing Ca2+ release from internal stores if receptor-activated Ca2+ entry from the extracellular space was prevented under Ca(2+)-free conditions or in the presence of La3+. This transmembrane current was abolished in the presence of intracellularly applied heparin. Depletion of Ins(1,4,5)P3-sensitive Ca2+ stores by internal application of Ins(1,4,5)P3 reduced the histamine evoked K+ current to some extent if the contribution of external Ca2+ was excluded.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Suramin reverses non-depolarizing neuromuscular blockade in rat diaphragm.

Unexpectedly, it was observed that the P2-purinoceptor antagonist, suramin (10 microM to 1 mM), reversed the muscle paralysis caused by structurally unrelated non-depolarizing relaxants. Suramin competitively reversed the blocking action of pancuronium. Both the pre- and postsynaptic blockade of nicotinic receptors by pancuronium was counteracted, as shown by the action of suramin, using train-of-four stimulation. Suramin did not affect the paralysis caused by the depolarizing relaxant, succinylcholine. The reversal action of suramin was not due to an increase in the acetylcholine concentration in the synaptic cleft, since neither the contraction of preparations partially paralysed by diminished acetylcholine release in the presence of low Ca2+ or high Mg2+ nor acetylcholinesterase activity were affected. Suramin did not affect the reduction in twitch tension caused by adenosine and potentiated the ATP-induced reduction in twitch, indicating that ATP-sensitive receptors are not involved in the reversal action of suramin. Consequently, these results suggest that the action of suramin is due to binding with a site on the acetylcholine receptor also occupied by non-depolarizing relaxants, but different from the site occupied by succinylcholine.

Acetylcholine↗
PubMed1992

Nucleotide receptors on DDT1 MF-2 vas deferens cells.

On exposure to triphosphatic nucleotides vas deferens DDT1 MF-2 smooth muscle cells responded with an outward K+ current as measured with the whole-cell patch clamp configuration. The rank order of potency was: ATP greater than UTP greater than TTP greater than CTP = GTP. The responses evoked by these agonists were blocked by suramin. Adenosine, ADP, alpha, beta-methylene-ATP and 2-methylthio-ATP did not affect the transmembrane current. The responses evoked by the nucleotides in DDT1 MF-2 cells are supposed to be mediated via 'nucleotide' receptors.

Adenosine Triphosphate↗
PubMed1992

Calcium release from separate receptor-specific intracellular stores induced by histamine and ATP in a hamster cell line.

1. The specificity of intracellular Ca2+ stores to Ca(2+)-mobilizing agonists was studied in DDT1 MF-2 vas deferens cells of the Syrian hamster. 2. Application of histamine (100 microM) or ATP (100 microM) to the DDT1 MF-2 cells caused an initial increase of intracellular Ca2+ followed by a lower phase as measured by using Indo-1 as fluorescent probe at 22 degrees C. The basal Ca2+ level (146 nM) was enhanced to 309 nM by histamine and to 379 nM by ATP. 3. A transient rise in intracellular Ca2+ lasting for about 2 min was measured in the presence of histamine or ATP in the absence of extracellular Ca2+. The basal Ca2+ level (78 nM) was increased to 128 nM by histamine and to 145 nM by ATP. 4. A transient hyperpolarization was elicited in single cells as measured with microelectrodes by both agonists under Ca(2+)-free conditions with a similar time course as the change in internal Ca2+. The hyperpolarization observed in the presence of histamine amounted to 23 mV and 31 mV with ATP. The histamine-induced responses were abolished by the H1 histaminoceptor antagonist mepyramine (10 microM) and the responses evoked by ATP were blocked by the P2 purinoceptor antagonist suramin (300 microM). 5. A second internal Ca2+ response could only be evoked under Ca(2+)-free conditions by applying a higher agonist concentration or after replenishing the intracellular stores with Ca2+ from the extracellular space. 6. A second addition of an optimal concentration (100 microM) of the agonist to the cells under Ca(2+)-free conditions did not evoke mobilization of internal Ca2+ or hyperpolarization, but resulted in a rise of the cellular inositol (1,4,5)-trisphosphate content (Ins(1,4,5)P3) as determined by a radioligand binding assay. 7. The cells responded to both agonists (100 microM) with a transient Ca2+ response if successively applied at a maximal effective concentration (100 microM) under Ca(2+)-free conditions. 8. Simultaneous stimulation of H1 histaminoceptors and P2 purinoceptors resulted in the absence of external Ca2+ in an additional increase in internal Ca2+ represented by the amplitude and area of the response and in an increased response area of the hyperpolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1991

Inositol phosphates formed in rat aorta after alpha 1-adrenoceptor stimulation are inhibited by forskolin.

Rat aortic smooth muscle rings without endothelial cells were subjected to alpha 1-adrenoceptor stimulation. We measured the contractile state of the smooth muscle cells and the formation of inositol phosphates (InsPs) on receptor stimulation. Using different extracellular calcium-containing solutions (2.5 mM, 0.1 mM and Ca(2+)-free) enabled us to discriminate three contractile phases after noradrenaline (10(-5) M) stimulation: an initial fast contraction (15 s) and a fast and slow component of the sustained contraction, which was established 10 min after stimulation. Under normal calcium conditions in the presence of 10 mM LiCl the formation of Ins(1,4,5)P3 was increased predominantly after stimulation, while the formation of Ins(1,3,4)P3, Ins(1,3,4,6)P4, Ins(1,3,4,5)P4, Ins(3,4,5,6)P4 and InsP5/InsP6 was also stimulated. The cAMP-inducing agent forskolin (0.5 microM) induced a relaxation of the basal tone and increased the level of the InsP4 isomers. The noradrenaline-induced contractile responses as well as the formation of InsP fractions mentioned were inhibited by forskolin. Further an increase in the formation of phosphatidylinositol bisphosphate was observed. It is concluded that in rat aorta InsPs and in particular Ins(1,4,5)P3 is involved in the different contractile phases caused by alpha 1-adrenoceptor stimulation. The relaxation induced by forskolin under these circumstances could be explained by an interaction of forskolin, most likely via the formation of cAMP, with InsPs formation at the level of phospholipase C activation.

Adrenergic alpha-Agonists↗
PubMed1991

Potassium channels regulated by inositol 1,3,4,5-tetrakisphosphate and internal calcium in DDT1 MF-2 smooth muscle cells.

This study was carried out to determine the intracellular components responsible for the transmembrane current evoked by stimulation of H1-histaminergic receptors in DDT1 MF-2 smooth muscle cells. Histamine elicited an outward current that was reversed below the K+ equilibrium potential and passed voltage-independent K+ channels. A histamine concentration-dependent rise in outward current and in cytoplasmic-free Ca2+ with similar time courses was observed. The histamine-induced current was not found after depletion of internal Ca2+ stores, suggesting a coupling between internal Ca2+ and K+ current. The time course of the initial increase in inositol (1,4,5)-trisphosphate (Ins (1,4,5)P3) caused by histamine differs from that of the internal Ca2+ response. However, a significant concentration-dependent increase in inositol (1,3,4,5)-tetrakisphosphate (Ins (1,3,4,5)P4) was seen during the whole stimulating period. The role of internal Ca2+, Ins (1,4,5)P3, and Ins (1,3,4,5)P4 on the outward current was also examined by the addition of these substances directly to the cytoplasm. Internal application of Ca2+ increased the amplitude and duration of the histamine-induced current whereas internal EGTA suppressed the outward current. Internal Ins (1,4,5)P3 did not affect the histamine-induced K+ current, Ins (1,3,4,5)P4 inhibited the outward current, and the combination of Ins (1,3,4,5)P4 and Ca2+ abolished this response. The noradrenaline response evoked under normal conditions is not reflected by a change in transmembrane current or a change in Ins (1,3,4,5)P4 but is associated with an increase in Ins (1,4,5)P3 and internal Ca2+. Stimulation of alpha 1-adrenoceptors, however, also evoked an outward current after the addition of Ins (1,3,4,5)P4 intracellularly. It is concluded that K+ channels, carrying the histamine outward current, are activated from the combined action of internal Ca2+ and Ins (1,3,4,5)P4.

Animals↗
PubMed1991

Generation of slow-wave-type action potentials in canine colon smooth muscle involves a non-L-type Ca2+ conductance.

1. The hypothesis was addressed that a non-L-type calcium conductance is involved in the generation of the initial part of the slow-wave-type action potential in the canine colon. 2. In the absence of a sodium and chloride gradient (NaCl replaced by glucamine), and in the presence of nitrendipine (in 'glucamine-nitrendipine' Krebs solution), a major portion of the upstroke potential of the slow wave persists at unchanged frequency. 3. In 'glucamine-nitrendipine' Krebs solution, the rate of rise and amplitude of the upstroke potential is reduced by removal of extracellular calcium in a concentration-dependent manner. 4. The rate of rise and the amplitude of the upstroke potential is in a concentration-dependent manner reduced by Ni2+ greater than Cd2+ greater than Co2+ greater than Mg2+. 5. In 'glucamine-nitrendipine' Krebs solution, Ba2+ cannot replace Ca2+ in the generation of the upstroke potential. 6. Positive evidence was obtained for the hypothesis that a non-L-type calcium conductance is involved in the initiation of the slow-wave-type action potential in colonic smooth muscle.

Action Potentials↗
PubMed1991

Effect of voltage and cyclic AMP on frequency of slow-wave-type action potentials in canine colon smooth muscle.

1. A non-L-type calcium conductance is involved in the generation of the initial part of the slow-wave-type action potential in colonic smooth muscle. The present study addresses the question whether this conductance is voltage or metabolically activated. 2. Current-induced hyperpolarization increased frequency and amplitude of slow waves measured in Krebs solution. 3. The upstroke potential was 'isolated' from the slow wave by superfusion with 'glucamine-nitrendipine' Krebs solution (NaCl was replaced by glucamine, nitrendipine was added). 4. Hyperpolarization up to -100 mV did not affect the upstroke potential frequency and increased its amplitude. Only hyperpolarization further than -100 mV decreased the frequency less than or equal to 20%, and reduced the amplitude less than or equal to 20%. 5. Depolarization did not affect the upstroke potential frequency. 6. Forskolin, but not 1,9-dideoxyforskolin dramatically decreased the upstroke potential frequency, without affecting other parameters including the resting membrane potential. 7. The effect of forskolin was mimicked by dibutyryl cyclic AMP, 8-bromo-cyclic AMP and 3-isobutyl-1-methylxanthine (IBMX), but not extracellular cyclic AMP. 8. The upstroke potential could not be evoked by depolarizing pulses after inhibition of activity by forskolin. 9. The effect of forskolin could be reversed by the calcium ionophore A23187. 10. In summary, voltage changes up to -40 mV and down to -100 mV do not, but changes in intracellular cyclic AMP do affect the frequency of the upstroke potential. 11. It is likely that intracellular metabolic activity, which may include cyclic AMP but not a voltage change, activates the conductance responsible for the generation of the upstroke potential.

Action Potentials↗
PubMed1990

P2-purinoceptor-activated membrane currents and inositol tetrakisphosphate formation are blocked by suramin.

The effect of suramin on the ATP-induced response in vas deferens DDT1 MF-2 smooth muscle cells was studied. Stimulation of P2-purinoceptors by ATP caused a change in membrane currents, measured by using the whole-cell patch-clamp configuration, and enhanced the formation of inositol phosphates, as analysed by high performance liquid chromatography. The ATP-induced membrane current consisted of a triphasic response, carried by a fast inward current, followed by a transient outward current and a sustained inward current. Inositol tetrakisphosphate (InsP4) formation increased in the presence of ATP. The formation of the isomers Ins(1,3,4,5)P4, Ins(1,3,4,6)P4 and Ins(3,4,5,6)P4 increased significantly after 5 min stimulation with ATP. Suramin inhibited the ATP-evoked membrane currents and the ATP-induced formation of inositol tetrakisphosphate isomers concentration dependently, but did not affect the basal inositol phosphate levels in the absence of ATP. These results indicate that suramin inhibits ATP-activated cellular processes in DDT1 MF-2 vas deferens cells, most likely by acting on P2-purinoceptors.

Adenosine Triphosphate↗
PubMed1989

Suramin and the inhibitory junction potential in taenia caeci of the guinea-pig.

The effect of surinam on the inhibitory junction potential evoked in smooth muscle cells of guinea-pig taenia caeci by stimulation of intramural nerves at 22 degrees C was investigated. The amplitude of the inhibitory junction potential was reduced concentration dependently by suramin. The suppression of this response by suramin became less pronounced when the number of stimuli increased (pulse rate: 20/s). These results indicate that suramin reduces the inhibitory junction response by interacting with P2-purinoceptors.

Adenosine Triphosphate↗
PubMed1989

P2-purinoceptor-mediated membrane currents in DDT1 MF-2 smooth muscle cells.

The electrophysiological response evoked by ATP was investigated in the DDT1 MF-2 smooth muscle cell line using the microelectrode technique and the whole-cell patch clamp technique. Application of ATP (10(-3) M) to the bathing solution caused a small initial depolarization of the cell membrane, followed by hyperpolarization and slow depolarization. During voltage clamping (-50 mV) a triphasic response was recorded on stimulation with ATP (10(-4)-10(-3) M). A short-lasting inward current was followed by a transient outward current and a slowly decreasing inward current. This response was not affected by the receptor antagonists, propranolol (3 X 10(-6) M), phentolamine (3 X 10(-6) M), atropine (3 X 10(-6) M) or theophylline (10(-3) M). The ATP-induced currents were not modified by the voltage-dependent channel blocking agents, tetraethyl ammonium (3 X 10(-3) M), 3,4-diaminopyridine (10(-3) M), tetrodotoxin (3 X 10(-7) M) or diltiazem (10(-5) M). The fast inward current was not detectable at a low ATP concentration (10(-5) M). The outward current showed a reversal potential near -76 mV, which equals the potassium equilibrium potential. This current was abolished after neutralization of the potassium electrochemical gradient. The outward current was suppressed under calcium-free conditions and also in the presence of tolbutamide (10(-4) M) or glipizide (5 X 10(-6) M). Guanosine triphosphate (5 X 10(-6) M) promoted the outward current, while this current was inhibited in the presence of guanosine diphosphate (5 X 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1989

Characterization of the UV-induced electrophysiological response in smooth muscle.

The effect of ultraviolet (UV) light on taenia caeci smooth muscle of guinea-pig was studied. This stimulus induced a decrease in membrane conductance, hyperpolarization of the smooth muscle cells, a decrease in spike activity and a diminished level of cGMP and enhancement of lipid peroxidation. The hyperpolarization evoked by UV light was attenuated in the presence of sodium nitrite, reaching a maximum at 0.5 mM sodium nitrite. The level of cGMP was enhanced in the presence of nitrite and lipid peroxidation was not changed. Under these conditions lipid peroxidation was not changed during UV irradiation either. The UV-induced hyperpolarization was abolished in the absence of extracellular calcium, inhibited in the presence of 8-Br-cGMP and enhanced by an increase in the extracellular calcium concentration. These results are consistent with the supposition that UV-A irradiation blocks calcium influx via a cGMP-dependent mechanism.

Animals↗
PubMed1989

Role of the sodium pump in pacemaker generation in dog colonic smooth muscle.

1. The role of the Na+ pump in the generation of slow wave activity in circular muscle of the dog colon was investigated using a partitioned 'Abe-Tomita' type chamber for voltage control. 2. Blockade of the Na+ pump by omission of extracellular K+, by ouabain, or the combination of 0 mM-Na+ and ouabain, depolarized the membrane up to approximately -40 mV and abolished the slow wave activity. Repolarization back to the control membrane potential by hyperpolarizing current restored the slow wave activity. 3. Slow waves continued to be present in 0 Na+, Li+ HEPES solution. 4. The depolarization induced by the procedures to block Na+ pump activity was associated with an increase in input membrane resistance. 5. Voltage-current relationships show the presence of an inward rectification. 6. Reduction of temperature depolarized the membrane, and decreased the slow wave frequency and amplitude. The slow wave amplitude was restored by repolarization of the membrane. 7. Brief depolarizing pulses evoked premature slow waves. Brief hyperpolarizing pulses terminated the slow waves. 8. We conclude that abolition of slow wave activity by Na+ pump blockade is a direct effect of membrane depolarization and that the Na+ pump is not responsible for the generation of the slow wave. 9. Our results are consistent with the hypothesis that pacemaker activity in smooth muscle is a consequence of membrane conductance changes which are metabolically dependent.

Animals↗
PubMed1989

Ionic basis of pacemaker generation in dog colonic smooth muscle.

1. The ionic basis of the slow waves in the circular muscle of the dog colon, in particular the ionic conductances involved in their initiation, were investigated by measuring intracellular electrical activity in the Abe-Tomita-type chamber for voltage control. 2. The depolarization that initiates the slow wave activity could be evoked by an increase in inward current and/or by a block of outward current. According to previous work, inward current could be carried by Na+, Cl-, and Ca2+ ions; K+ ions would carry outward current. 3. The Na+ channel blocker tetrodotoxin (5 x 10(-7) M) did not affect the slow wave amplitude nor its rate of rise. After omission of Na+, by replacing Na+ with N-methyl-D-glucamine, large slow waves continued to develop although some changes in slow wave characteristics occurred. 4. Replacement of 91% of the Cl- by isethionate decreased the slow wave frequency and increased the slow wave amplitude. However, NaCl substitution by sucrose increased the slow wave frequency and decreased the slow wave amplitude. 5. Slow wave activity continued to develop after blockade of Ca2+ influx by D600 (10(-6) M) or CoCl2 (1-3 mM). D600 and Co2+ did not affect the membrane potential but reduced the slow wave amplitude and abolished the plateau potential. Slow waves were abolished after omission of extracellular Ca2+ (plus 1 mM-EGTA). This suggests that Ca2+ influx is probably not necessary but extracellular presence of Ca2+ ions is indispensible for the slow wave generation. 6. The combination of 0 Na+, Li+ HEPES solution, by replacing Na+ with Li+, plus D600 depolarized the cells (up to approximately -40 mV) and abolished slow wave activity. This effect was voltage dependent since repolarization caused slow waves to return. 7. Abolition of the slow wave activity was also obtained by current-induced depolarization to approximately -40 mV. However, during high-K+-induced depolarization (to approximately -40 mV) high amplitude (16 mV) slow waves were still present, slowing that the voltage dependence of the slow waves was shifted positively. This effect probably occurs due to modification by extracellular K+ of a voltage-dependent K+ conductance, which would suggest that a K+ conductance is involved in slow wave generation. 8. In conclusion, slow waves are generated by cyclic membrane conductance changes, which are dependent on the presence of extracellular Ca2+ ions and on the membrane potential. Our data are consistent with the hypothesis that slow waves are initiated by the blockade of a K+ conductance.

Animals↗
PubMed1988

The multiple action of bradykinin on smooth muscle of guinea-pig taenia caeci.

The action of bradykinin on the smooth muscle of guinea-pig taenia caeci was studied by measuring changes in membrane potential, the contractile state of the muscle cells and intracellular calcium concentrations at 22 degrees C in the presence of tetrodotoxin, yohimbine, prazosin, propranolol and atropine. The bradykinin response was characterised by an initial hyperpolarization and suppression of spike activity followed by a sustained depolarization and an increased spike activity accompanied by inhibition of the phasic contractions, an increase in muscle tone and the development of phasic contractions, respectively. The actions of bradykinin were not affected after B1-bradykinin receptors were blocked with des-Arg9-[Leu8]bradykinin. The events induced by bradykinin were accompanied by an increase in the intracellular calcium concentration, as monitored by quin-2 fluorescence. The hyperpolarization and depolarization persisted in the presence of diltiazem (10(-5) M) and in calcium-free conditions. The hyperpolarization could be evoked only once in the absence of calcium and was inhibited in the presence of apamin and after stimulation of alpha 1-adrenoceptors or P2-purinoceptors. Membrane conductance was decreased during the sustained depolarization. The membrane depolarization was abolished after the sodium concentration gradient was reduced. These results show a multiple action of bradykinin mediated via B2-receptors: (1) on calcium mobilization associated with activation of potassium channels; (2) on calcium release from intracellular stores and (3) on receptor-activated sodium channels.

Animals↗