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61.
G. Matthijs T. L. Peeters G. Vantrappen 《Naunyn-Schmiedeberg's archives of pharmacology》1989,339(3):332-339
Summary The contraction of longitudinal muscle strips of the rabbit duodenum in response to motilin and acetylcholine was investigated in normal and high K+-solutions in the presence and absence of external calcium, in order to demonstrate the existence of pharmaco-mechanical coupling for motilin and to examine whether the peptide mobilizes calcium from an intracellular store. In depolarized smooth muscle (140 mM K+), motilin (3.2×109 –1×10–7 M) and acetylcholine (1×10–5 M) were still capable of causing a considerable, transient, concentration-dependent contraction in the presence of Ca2+. The extra-contraction to motilin was not blocked by tetrodotoxin (1 g/ml) nor by atropine (10–7 M), but acetylcholine (10–5 M) was blocked by atropine. Verapamil (10–7 M) could selectively block the K+ contraction without affecting the extra agonist contraction. Nitroprusside was ineffective up to 10–4 M in high K+-solutions, but in normal Hepes-buffer it caused a concentration-dependent rightward shift of the concentration-response curve of motilin and acetylcholine contractions. In a calcium-depleted medium, high K+-depolarized muscle strips were still responsive to motilin and acetylcholine, but higher concentrations (10–6 M) were needed than in the presence of calcium and the contractions reached only 57 +- 11% and 74 +- 9% respectively of the maximal contraction in 1.2 mM Ca2+ containing solutions. The response to motilin (10–6 M) was not only smaller than that to acetylcholine (10–5 M), it also faded more rapidly with time. The response to one agonist could not be repeated except by using a higher concentration of the same or the other agonist, and the magnitude of this second response depended upon the dose used in the first one. We conclude that pharmaco-mechanical coupling exists for motilin and that this peptide is able to elicit contractions by mobilization of calcium from an intracellular store. This store overlaps with the one used by acetylcholine. Our experiments also reinforce the hypothesis that in the rabbit motilin exerts a direct action upon smooth muscle cells. 相似文献
62.
Alexander Mülsch Eberhard Bassenge Rudi Busse 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(6):767-770
Summary Release of nitric oxide (NO) from endothelial cells critically depends on a sustained increase in intracellular free calcium maintained by a transmembrane calcium influx into the cells. Therefore, we studied whether the free cytosolic calcium concentration directly affects the activity of the NO-forming enzyme(s) present in the cytosol from freshly harvested porcine aortic endothelial cells. NO was quantified by activation of a purified soluble guanylate cyclase coincubated with the cytosol. In the presence of 1 mM L-arginine, 0.1 mM NADPH and 0.1 mM EGTA, endothelial cytosol (0.2 mg of cytosolic protein per ml) stimulated the activity of guanylate cyclase 5.0 + 0.5-fold (from 31 + 9 to 153 + 15 nmol cyclic GMP formed per min per mg guanylate cyclase). Calcium chloride increased this stimulation further in a concentration-dependent fashion by up to 136 + 15% (with 2 M free calcium; EC50 0.3 M). The calcium-dependent and -independent activation of guanylate cyclase was enhanced by superoxide dismutase (0.3 M) and was inhibited by the stereospecifically acting inhibitor of L-arginine-dependent NO formation NG-nitro-L-arginine (1 mM) and by LY 83583 (1 M), a generator of superoxide anions. Our findings suggest a calcium-dependent and -independent synthesis of NO from L-arginine by native porcine aortic endothelial cells.
Send of fprint requests to A. Mülsch, at the above address 相似文献
63.
A hepatic soluble aldehyde dehydrogenase (ALDH), inducible by polycyclic aromatic hydrocarbons, was studied in Wistar rats in connection with substances known to affect drug metabolism or aldehyde dehydrogenase activity, such as phenobarbital (PB), disulfiram (DS), -diethylaminoethyl diphenylpropylacetate (SKF 525A) and calcium cyanamide (CC). 3-Methylcholanthrene (MC) was given as a model inducer of ALDH (100 mg/kg, i.p., as a single dose) and the animals were killed after 3 days. Pretreatment with PB (1 g/l drinking water, for 2 weeks) enhanced the inducing effect of MC. On the contrary, pretreatment with DS (100 mg/kg, i.p., daily x4) reduced by 70% the expected increase in ALDH activity. Neither SKF 525A (25 mg/kg, i.p., daily x4), nor CC (5 mg/kg, i.p., daily x4) could affect the action of the inducer. At the above doses, basal ALDH activity was inhibited by DS (30%) and CC (70%), but was not affected at all by PB or SKF 525A. The results were somewhat different when the various effectors tested were administered to animals already treated with MC (20 mg/kg, i.p., daily x6). In this case, DS did not affect the already induced ALDH activity. On the contrary, CC was still an effective inhibitor. Unexpectedly, post-treatment with SKF 525A further enhanced the initial induction brought about by MC. Our findings show that substances affecting microsomal drug metabolism can interfere with the process of ALDH induction by MC. The additive result of PB pretreatment is probably due to the enhanced accumulation of an active metabolite of MC. The opposite effect of DS on drug metabolism could explain the decreased ability of MC to induce ALDH activity. The MC-inducible ALDH isozyme can be effectively inhibited with CC, but not with DS. 相似文献
64.
Since previous studies showed that calcium uptake by synaptosomes from rodents declines with aging [30], the subsynaptosomal distribution of calcium was determined with the disruption method of Scott et al. [37]. Calcium uptake by the mitochondrial (digitonin-resistant) and non-mitochondrial (digitonin-labile) compartments, as well as total uptake, were determined at 2, 5 and 10 min. After a 10 min incubation under resting conditions (5 mM-KCl), total calcium uptake decreased at 10 months (−14.6%) and 30 months (−33.0%) of age; mitochondrial calcium uptake increased by 10 months (+11.2%) but declined by 30 months (−17.5%); the nonmitochondrial calcium compartment declined at 10 (−34.7%) and 30 (−43.4%) months when compared to the 3 month old control. With potassium depolarization (31 mM-KCl), total calcium uptake declined from 100% (3 months) to 73.8% (10 months) or 53.0% (30 months); mitochondrial calcium uptake declined from 100% (3 months) to 85.6% (10 months) or 68.4% (30 months); non-mitochondrial calcium uptake decreased at 10 (−34.3%) and 30 (−57.7%) months of age when compared to 3 months (100%). The deficits in calcium homeostasis are not due to changes in synaptosomal volumes or to diminished membrane potentials, as assessed by tetraphenylphosphonium ion accumulation. 3,4-Diaminopyridine partially reversed the alterations in total, mitochondrial and non-mitochondrial calcium uptake by synaptosomes from aged mice. 相似文献
65.
W. Walz A. F. Allen 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1987,68(2):290-298
Summary Homogenous primary cultures of mouse astrocytes and cortical neurons were used to clarify the role of taurine in ion and osmoregulation in the CNS. This study indicates that both neurons and glial cells have uptake systems for taurine. The cell water content does not change during loading of cells with taurine. Chemical analysis indicates that part of the accumulated taurine is metabolized and that the product(s) are stored in the cells. Extracellular taurine (1 mM) has no effect on K+, Na+, Cl-, or Ca2+ movements in astrocytes. However, astrocytes loaded to a taurine content which corresponds a concentration of 60 mM (corresponds to normal mouse cortex levels) show a 50% reduction in their K+ accumulation by carriers and a 100% increase in Ca2+ turnover rates. Movements of Ca2+ and K+ are involved in neurotransmission. It appears that taurine stored in glial cells, has an important effect on ion homeostasis in the CNS and may act indirectly on neuronal excitability. 相似文献
66.
Kotoko Sumimoto Hirosi Kuriyama 《Pflügers Archiv : European journal of physiology》1986,406(2):173-180
Ca2+ mobilization in dispersed smooth muscle cells of the porcine coronary artery was investigated using the fluorescent Ca2+ indicator, quin2. The resting [Ca2+]i was 113±8 nM (a mean±SE), and was independent of intracellular quin2 concentrations. Acetylcholine (ACh; over 10 nM) or caffeine (over 3 mM) transiently increased the intensity of fluorescence, thereby reflecting the elevation of intracellular free Ca2+ (Ca2+ transient), while excess K+ gradually increased and maintained the intensity of fluorescence. Application of EGTA reduced the resting intensity of the fluorescence and blocked the K+-induced Ca2+ transient, but did not supress the Ach-or caffeine-induced ones. Nisoldipine (0.1 M) did not affect the resting intensity of the fluorescence. This agent blocked the K+ induced but not the ACh-or caffeine-induced Ca2+ transient. Thus, sources of Ca2+ contributing to the K+-induced Ca2+ transient differ from those evoked by other agents. The amount of Ca2+, as estimated from the increased Ca2+ transient by caffeine or ACh, was increased in proportion to the excess K+-induced influx of Ca2+. 相似文献
67.
P. J. Griffiths J. J. Duchateau Y. Maeda J. D. Potter C. C. Ashley 《Pflügers Archiv : European journal of physiology》1990,415(5):554-565
Intact muscle fibres fromBalanus nubilus develop tensions of up to 600 kN sd m−2 during electrical stimulation. The rise of tension occurs with a half-time (177 ms at 12° C) about fivefold longer than that
of tetanised frog muscle at the same temperature. The response of myofibrillar bundles to a rapid stretch resembles that of
frog muscle but has a yo value (i.e. the size of an instantaneous release necessary to just discharge tension) which is ca. 2.5 times smaller, and
phase 2 of the tension transient (the “quick phase”) occurs at a rate comparable to that of frog muscle. In contrast, the
ATPase activity (0.018 mmoles · kg wet weight−1 · s−1) of this preparation and its maximum shortening velocity (0.15–0.16 muscle lengths · s−1) are both at least fivefold slower than frog muscle. These findings can be accounted for by a cross-bridge cycle in barnacle
muscle in which events prior and subsequent to the tension generating step(s) occur at a rate at least fivefold slower than
comparable steps in frog muscle, but the step(s) associated with tension development occur at similar rates in the two preparations.
Since the rate of mechanical relaxation in barnacle muscle is modified in the presence of intracellular calcium buffers and
by depolarisation-induced elevation of the free calcium during the relaxation phase, it is proposed that the time course of
relaxation is not determined exclusively by the kinetics of the cross-bridge cycle, but is also dependent on the free calcium
concentration during relaxation. 相似文献
68.
本文探讨了5/6肾切除术后慢性肾衰大鼠残肾纤维化的发生机理,发现术后120天,在残肾单个核炎性细胞浸润、残肾显著纤维化和肾功能损害的同时,残肾脂质过氧化物含量显著升高,抗氧化机制功能显著下降,钠钾ATP酶活力显著下降,周围血单个核细胞内游离钙浓度显著升高,单个核细胞培养上清白介素-1活性增高。而摄入大量维生素E的大鼠,上述各指标有不同程度的改善,残肾纤维化显著减轻。提示残肾纤维化可能与单个核白细胞内游离钙浓度升高,进而产生白介素-1增多有关。 相似文献
69.
Bernd Sutor Walter Zieglgänsberger 《Pflügers Archiv : European journal of physiology》1987,410(1-2):102-111
Intracellular recordings were obtained from rat neocortical neurons in vitro. The current-voltage-relationship of the neuronal membrane was investigated using current- and single-electrode-voltage-clamp techniques. Within the potential range up to 25 mV positive to the resting membrane potential (RMP: –75 to –80 mV) the steady state slope resistance increased with depolarization (i.e. steady state inward rectification in depolarizing direction). Replacement of extracellular NaCl with an equimolar amount of choline chloride resulted in the conversion of the steady state inward rectification to an outward rectification, suggesting the presence of a voltage-dependent, persistent sodium current which generated the steady state inward rectification of these neurons. Intracellularly injected outward current pulses with just subthreshold intensities elicited a transient depolarizing potential which invariably triggered the first action potential upon an increase in current strength. Single-electrode-voltage-clamp measurements reveled that this depolarizing potential was produced by a transient calcium current activated at membrane potentials 15–20 mV positive to the RMP and that this current was responsible for the time-dependent increase in the magnitude of the inward rectification in depolarizing direction in rat neocortical neurons. It may be that, together with the persistent sodium current, this calcium current regulates the excitability of these neurons via the adjustment of the action potential threshold. 相似文献
70.
D. Dory C. Chopin I. Aimone-Gastin J. L. Gueant L. Guerin J. Sainte-Laudy D. A. Moneret-Vautrin J. Fleurence 《Allergy》1998,53(1):42-50
Allergy to fish is one of the most common food allergies. Gad c 1 is the only fish allergen which has been purified and characterized. Other allergens have been detected by Western blot in cod extracts. We have now improved the Western-blot procedure in order to characterize fish IgE-reactive proteins from extracts prepared under different conditions: pre-rigor mortis and postrigor mortis. EDTA addition or not. and DEAE ion-exchange chromatography. Several IgE-reactive protein bands have been identified over a wide molecular-weight range. In particular, the 104- and 130-kDa IgEreactive protein bands were detected. These new bands may correspond to aggregates, as EDTA increased the relative amount of the 60-, 67-, 104-, and 130-kDa IgE-reactive protein bands in Western blot. All these bands were also detected by an antiparvalbumin monoclonal antibody, specific to the first calcium-binding site. The longer period of storage increased the relative amounts of the 41-, 80-, 104-. and 130-kDa IgE-reactive protein bands. The 18-kDa band was detected only in fish stored for several days. In conclusion, we have described IgE-reactive protein bands over a wide molecular-weight range (12–130 kDa) in Western blot of cod extract, and shown that EDTA and storage conditions may influence the relative distribution of IgE-reactive protein bands. 相似文献