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31.
The effects of 4-aminopyridine (4-AP) were studied on isolated papillary muscles from the heart of reserpinized rabbits (at 37°C). The preparations were paced to contract at 0.67 Hz under isometric conditions and the muscle length was adjusted to 95 % of the length for optimum force production. Simultaneous recordings of isometric force and membrane potentials were performed. 4-AP (50 μM) increased peak force by approximately 20% of the control and prolonged the action potential by 20%. Higher concentrations of 4-AP (800 μ.M) resulted in further increments of force and action potential duration (60 and 70% of controls, respectively). Prolongation of the action potential and potentiation of the isometric force was still present one hour after withdrawal of the drug from the perfusate. The results are consistent with the view that 4-AP prolongs the action potential by inhibiting the late repolarizing potassium current. It is suggested that the calcium uptake by the ventricular cell during the prolonged action potential is increased and that this leads to the positive inotropic effect. 相似文献
32.
Bendicht U. Pauli Hellmut G. Augustin-Voss Marwan E. El-Sabban Robert C. Johnson Daniel A. Hammer 《Cancer metastasis reviews》1990,9(3):175-189
Summary The initial, site-specific colonization of secondary organs by blood-borne cancer cells appears to be mediated by endothelial cell adhesion molecules. These molecules are part of the organ-specific microvascular phenotype and are regulated through complex interactions of the endothelium with the extracellular matrix (e.g., distinct matrix macromolecules and growth factors). They are inducedin vitro by growing unspecific (large vessel) endothelial cells on extracts of organ-specific biomatrices. In many respects, these molecules are similar to the various classes of chemically different adhesion molecules that regulate lymphocyte traffic, but are believed to be distinct from the inducible adhesion molecules that govern leukocyte adhesion during acute episodes of inflammation. Biochemical and biophysical data indicate that preference of tumor cell adhesion to organ-specific microvascular endothelium may not require qualitative differences of such homing receptors between endothelia, but may be explained on the basis of quantitative receptor differences as well as differences of receptor avidity. Following adhesion, the metastatic cascade proceeds by the establishment of metabolic conduits between the endothelium and adherent tumor cells. This heterotypic coupling represents an early step in the extravasation of cancer cells from the microvasculature, initiating endothelial cell retraction from its basement membrane and recanalization around the arrested tumor cell. These events, together with local growth promoting effects exerted by the metastasized organ, are believed to provide the basis for Paget's seed and soil hypothesis of metastasis. 相似文献
33.
Giorgio Rizzo Carola Ricciardelli Eloisa Sardella Roberta Musio Marco Lo Presti Danilo Vona Fiorenzo G. Omenetto Gianluca Maria Farinola 《Macromolecular chemistry and physics.》2023,224(21):2300145
Bombyx mori silk fibroin (SF) is a very versatile biopolymer due to its biocompatibility and exceptional mechanical properties which make possible its use as a functional material in several applications. SF can be modified with a large variety of chemical approaches which endow the material with tailored chemical–physical properties. Here, a systematic investigation of different routes is reported to graft long alkyl chains on SF based on both liquid- and solid-phase, aiming to modulate its hydrophobic behavior. The liquid phase method involves direct activation of SF tyrosine residues via diazo coupling and cycloaddition reactions, generating hydrophobic materials insoluble in any common solvent. The solid phase approach consists of the chemical modification of drop-casted SF films by esterification of hydroxyl groups of serine, threonine, and tyrosine SF residues with acyl chlorides of fatty acids. For the solid-state functionalization, a new class of hydrophobic pendant groups is synthesized, based on triple esters of gallic acid anhydrides, that are reacted with the biopolymer to further enhance its resulting hydrophobic features. 相似文献
34.
An efficient synthesis of 3-(E)-hydroxy- and 3-(E)-acetoxypropenylcephem derivatives, key intermediates for the synthesis of 3-(E)-propenylcephalosporins was achievedvia Stille coupling reaction of 3-trifloxycephem with 3-(E)-tributylstannylallylic alcohol. 相似文献
35.
- To characterize increases in cytosolic free Ca2+ concentration ([Ca2+]i) associated with discharge of action potentials, membrane potential and [Ca2+]i were simultaneously recorded from single smooth muscle cells of guinea-pig ileum by use of a combination of nystatin-perforated patch clamp and fura-2 fluorimetry techniques.
- A single action potential in response to a depolarizing current pulse elicited a transient rise in [Ca2+]i. When the duration of the current pulse was prolonged, action potentials were repeatedly discharged during the early period of the pulse duration with a progressive decrease in overshoot potential, upstroke rate and repolarization rate. However, such action potentials could each trigger [Ca2+]i transients with an almost constant amplitude.
- Nicardipine (1 μM) and La3+ (10 μM), blockers of voltage-dependent Ca2+ channels (VDCCs), abolished both the action potential discharge and the [Ca2+]i transient.
- Charybdotoxin (ChTX, 300 nM) and tetraethylammonium (TEA, 2 mM), blockers of large conductance Ca2+-activated K+ channels, decreased the rate of repolarization of action potentials but increased the amplitude of [Ca2+]i transients.
- Thapsigargin (1 μM), an inhibitor of SR Ca2+-ATPase, slowed the falling phase and somewhat increased the amplitude, of action potential-triggered [Ca2+]i transients without affecting action potentials. In addition, in voltage-clamped cells, the drug had little effect on the voltage step-evoked Ca2+ current but exerted a similar effect on its concomitant rise in [Ca2+]i to that on the action potential-triggered [Ca2+]i transient.
- Similar action potential-triggered [Ca2+]i transients were induced by brief exposures to high-K+ solution. They were not decreased, but rather increased, after depletion of intracellular Ca2+ stores by a combination of ryanodine (30 μM) and caffeine (10 mM) through an open-lock of Ca2+-induced Ca2+ release (CICR)-related channels.
- The results show that action potentials, discharged repeatedly during the early period of a long membrane depolarization, undergo a progressive change in configuration but can each trigger a constant rise in [Ca2+]i. Intracellular Ca2+ stores have a role, especially in accelerating the falling phase of the action potential-triggered [Ca2+]i transients by replenishing cytosolic Ca2+. No evidence was provided for the involvement of CICR in the action potential-triggered [Ca2+]i transient.
36.
The effects of caffeine on cytoplasmic Ca2+ oscillations induced by carbachol and guanosine 5-O-(3-thiotriphosphate) (GTP--S) were studied in individual mouse pancreatic ß-cells clamped at a hyperpolarized potential. Addition of 10 mM caffeine did not affect the cytoplasmic Ca2+ concentration ([Ca2+]1) in ß-cells exposed to 20 mM glucose and hyperpolarized with diazoxide. Under similar conditions 100 M carbachol induced a typical response with a marked [Ca2+]i peak followed by a lower sustained elevation. Irrespective of whether 10 mM caffeine was present, there were [Ca2+]i transients with frequencies of 1–5/min superimposed on the sustained phase in 50–60% of the cells. In previously non-exposed cells the introduction of 10 mM caffeine caused temporary lowering of the sustained phase with disappearance of the transients. Subsequent omission of caffeine in the continued presence of carbachol caused a marked [Ca2+]i peak followed by reappearance of the [Ca2+]i, transients. However, in cells oscillating in the presence of caffeine its omission caused disappearance of the transients. In this case reintroduction of caffeine restored the transients.In cells kept at –70 mV by a patch pipette containing 100 M GTP--S and 3 mM Mg-ATP there were [Ca2+]i transients with frequencies of 0.5–2.5/min. These transients were sufficiently pronounced to activate repetitively a K+ current. Addition of 10 mM caffeine caused disappearance of the [Ca2+]i transients or reduction of their amplitudes and frequencies.The results indicate that caffeine does not activate Ca2+-induced Ca2+ release in hyperpolarized ß-cells but inhibits the Ca2+-mobilizing effect of inositol 1,4,5-trisphosphate.
Correspondence to: E. Gylfe at the above address 相似文献
37.
Rajiv Kumar Ronald W. Joyner 《Pflügers Archiv : European journal of physiology》1994,428(5-6):425-432
An ischemic myocardial region contains cells with a depolarized resting membrane potential. This depolarization leads to an intercellular current flow between the ischemic region and the surrounding normal myocardial cells which has been termed an injury current. We have devised an experimental model system in which an isolated guinea pig ventricular cell is electrically coupled to a model depolarized cell in order to evaluate the effects of this injury current on the electrical properties of a normal ventricular cell exposed to drugs which increase calcium current or decrease potassium current. Using low doses of isoproterenol, forskolin, or Bay K 8644 (or 8-bromo-cyclic adenosine monophosphate in the pipette) we found that the action potential duration of the isolated cell was lengthened, but that early after depolarizations (EADs) were not produced unless the cell was also coupled to a depolarized cell model representing an adjacent ischemic region. A similar prolongation of the action potential was produced by low doses of quinidine, but EADs were not produced unless coupling to a depolarized cell model was added. EADs could not be produced in any cells in the absence of the drugs even though the coupling to the depolarized cell model was increased up to the level at which the action potential was indefinitely prolonged. At higher isoproterenol concentrations, EADs or spontaneous activity were produced without coupling to the depolarized cell model. Under these conditions, coupling of the cell to a cell model with normal resting membrane potential stopped the spontaneous activity and prevented the occurrence of EADs even with high levels of resistive coupling. These findings suggest that the electrotonic influences of a localized depolarized region can produce EADs if the calcium current magnitude is increased, which would be the case for sympathetic innervation. 相似文献
38.
Summary The effects ofd-sotalol on intercellular electrical coupling and ultrastructure under hypoxic conditions were investigated in myocardial samples from eight young (1–2 months) and four older (10–12 months) guinea pigs. A right ventricular muscle strip was kept simultaneously in two divided chambers and superfused with normoxic and/or hypoxic (97% N2+ 3% CO2) Krebs solution. Hypoxia caused shortening of action potential duration (APD) and electrical cellto-cell uncoupling. If the uncoupling appeared after short-term hypoxia (less than 30 min), administration of 3.10–7M ofd-sotalol to the hypoxic perfusate led to a recovery of electrical coupling. Transmission electron microscopy revealed moderate reversible ultrastructural alterations of the cardiomyocytes. No apparent changes in intercellular junctions were observed. The recoupling effect of sotalol decreased with the time of hypoxia as the ultrastructural damage progressed. After prolonged hypoxia (more than 30min), cardiomyocytes were markedly injured, intercellular junctions were severely affected, and gap junctions occurred less frequently. In these cases, administration ofd-sotalol caused only transient recoupling. After 1h of hypoxia, no recoupling was observed. Pretreatment withd-sotalol prevented hypoxia-induced electrical uncoupling and markedly attenuated ultrastructural damage, although shortening of APD still persisted. Our results indicate that the cardioprotective effect ofd-sotalol on electrical intercellular coupling is closely associated with sotalol-induced prevention of the ultrastructural damage. Considering previous results, we suggest that this protective effect ofd-sotalol may be related to its ability to increase intracellular cyclic adenosine monophosphate and, thereby, to decrease cytosolic free Ca. These effects can explain the antiarrhythmic and defibrillating properties ofd-sotalol. 相似文献
39.
T. L. Peeters G. Matthijs G. Vantrappen 《Naunyn-Schmiedeberg's archives of pharmacology》1991,343(2):202-208
Summary Recent studies suggested that certain erythromycin A (EM-A) derivatives are motilin receptor agonists. As proposed by Itoh they may be called motilides. We have investigated the Ca2+-dependence of contractions induced by two potent motilides, ME-34 [de(N-methyl) 8,9-anhydroeryhtromycin A 6,9-hemiacetal] and EM-523 [de(N-methyl)-N-ethyl-8,9-anhydro-erythromycin A 6,9-hemiacetal], in duodenal tissues and compared the results with those previously obtained with motilin.Isometric and isotonic contractile responses of isolated longitudinal muscle sheets from the rabbit duodenum were tested under normal, Ca2+-free and depolarizing conditions. Prior to stimulation with motilides, the maximal response to acetylcholine was recorded and all responses were always expressed as a percentage of this response. Both motilides induced contractions in normally polarized tissue, with an EC50 of 26 ± 5 nM for ME-34 (n = 7), and 27 ± 5 nM for EM-5231 (n = 16) and maximal responses of respectively 88 ± 4% and 80 ± 3%. Like motilin, both compounds induced an extra-contraction in depolarized tissues. The EM-523 response in 140 mM K+under isotonic conditions was 84 ± 3% (n = 5) at 10–5
M, with an EC50 that was shifted to 65 ± 18 nM. Similar figures were obtained for ME-34. When Ca2+ was added to Ca2+-depleted strips, half-maximal Ca2+ values (in mM) were 1.10 ± 0.11 (n = 9) for EM-523 and 1.13 ± 0.12 (n = 3) for ME-34, as compared with 1.12 ± 0.13 (n = 7) for motilin and 2.8 ± 1.1 (n = 9) for K+. Both ME-34 and EM-523 also induced a transient contraction in Ca+-free solutions under isometric conditions. The response to EM-523 (5 × 10–6
M) was 49 ± 15% (n = 4) after 3 min. A maximal EM-523 -stimulation reduced a subsequent ACh response by 78 ± 7%, whereas EM-523 and ME-34 could not induce a contraction after ACh.We conclude that motilides depend upon external Ca2+ to a similar extent to motilin. Like motilin, they are also able to mobilize intracellular Ca Z + stores. Our results support the hypothesis that motilides act on motilin receptors.
Send offprint requests to T. L. Peeters at the above address 相似文献
40.
《Journal of labelled compounds & radiopharmaceuticals》2003,46(4):333-342
A new approach for 11C–C bond formation via a Sonogashira‐like cross‐coupling reaction of terminal alkynes with [11C]methyl iodide was exemplified by the synthesis of 17α‐(3′‐[11C]prop‐1‐yn‐1‐yl)‐3‐methoxy‐3,17β‐estradiol. The LC‐purified title compound was obtained in decay‐corrected radiochemical yields of 27–47% (n=8) based on [11C]methyl iodide within 21–27 min after EOB. In a typical synthesis starting from 9.6 GBq [11C]methyl iodide, 1.87 GBq of 17α‐(3′‐[11C]prop‐1‐yn‐1‐yl)‐3‐methoxy‐3,17β‐estradiol was synthesized in radiochemical purity >99%. The specific radioactivity ranged between 10 and 19 GBq/µmol, and the labeling position was verified by 13C‐NMR analysis of the corresponding 13C‐labeled compound. Copyright © 2003 John Wiley & Sons, Ltd. 相似文献