0000000000060538
AUTHOR
H. Nawrath
Discoordinate regulation of different K channels in cultured rat skeletal muscle by nerve growth factor
We investigated the effects of nerve growth factor (NGF) on expression of K+ channels in cultured skeletal muscle. The channels studied were (1) charybdotoxin (ChTx)-sensitive channels by using a polyclonal antibody raised in rabbits against ChTx, (2) Kv1.5 voltage-sensitive channels, and (3) apamin-sensitive (afterhyperpolarization) channels. Crude homogenates were prepared from cultures made from limb muscles of 1-2-day-old rat pups for identification of ChTx-sensitive and Kv1.5 channels by Western blotting techniques. Apamin-sensitive K+ channels were studied by measurement of specific [125I]-apamin binding by whole cell preparations. ChTx-sensitive channels display a fusion-related incr…
Excitotoxic Hippocampal Membrane Breakdown and its Inhibition by Bilobalide: Role of Chloride Fluxes
We have previously shown that hypoxia and N-methyl-D-aspartate (NMDA) receptor activation induce breakdown of choline-containing phospholipids in rat hippocampus, a process which is mediated by calcium influx and phospholipase A (2) activation. Bilobalide, a constituent of Ginkgo biloba, inhibited this process in a potent manner (Weichel et al., Naunyn-Schmiedeberg's Arch. Pharmacol. 360, 609-615, 1999). In this study, we used fluorescence microscopy and radioactive flux measurements to show that bilobalide does not interfere with NMDA-induced calcium influx. Instead, bilobalide seems to inhibit NMDA-induced fluxes of chloride ions through ligand-operated chloride channels. In our experimen…
Papaverine enhances the negative inotropic effect of acetylcholine in rat auricles
The negative inotropic effect of acetylcholine in rat left auricles is enhanced in the presence of the phosphodiesterase inhibitor papaverine. This result favours the idea of a cyclic GMP-mediated action of acetylcholine in the heart.
Opposite effects of beta-adrenoceptor stimulation and 8-bromo-cyclic AMP on potassium efflux in mammalian heart muscle.
beta-adrenoceptor stimulation by isoprenaline increases the potassium efflux in beating guinea-pig atria. This effect is not mimicked by 8-bromo-cyclic AMP, a cyclic AMP analogue which exerts a positive inotropic effect in this preparation.
Tetrodotoxin slightly shortens action potential duration in ventricular but not in atrial heart muscle.
Tetrodotoxin (TTX), at concentrations significantly decreasing maximal upstroke velocity (dV/dtmax) of the action potential, exerted variable effects on action potential duration (APD) in different myocardial preparations. APD was virtually unchanged by tetrodotoxin in the guinea pig atrium, but slightly shortened in the guinea pig ventricle at maximally effective concentrations. In the human ventricle, both dV/dtmax and APD were reduced in the same concentration range of TTX. These results suggest that a TTX-sensitive sodium current significantly contributes to the repolarization phase of the action potential in ventricular but not in atrial heart muscle.
A negative inotropic effect of acetylcholine in the presence of several phosphodiesterase inhibitors.
The phosphodiesterase inhibitors papaverine, theophylline and 3-isobutyl-1-methylxanthine (IBMX) reveal a negative inotropic effect of acetylcholine in cat ventricular heart muscle. This effect in unrelated to beta-adrenoceptor stimulation and possibly mediated by the accumulation of cyclic GMP.
Effects of Some Directly-Acting Smooth Muscle Relaxant Drugs on Isolated Human Preparations of the Upper Urinary Tract
It is generally assumed that drugs which induce relaxation of smooth muscles may be of clinical importance in some urological disorders; such drugs are indeed widely used, for example in the therapy of unstable bladders or to facilitate the passage of ureteral stones. Antispasmodic action may be classified in neurotropic and musculo-tropic action; the former acting on the autonomic nervous system and the latter directly on smooth muscle cells. Examples for the first type of action are anticholinergic drugs or alpha-adrenoceptor-antagonists, whereas papaverine is a classic drug with the second type of action.
Mechanical and electrophysiological effects of cromakalim on the human urinary bladder.
The effects of cromakalim on spontaneous and induced mechanical activity of human detrusor muscle were investigated in vitro. Cromakalim produces a concentration-related decrease of spontaneous as well as carbachol- and K(+)-evoked contractions. This is the first study to utilize the patch clamp technique to elucidate the mechanism of action of cromakalim on human detrusor cells. Cromakalim hyperpolarizes the detrusor cells by increasing the net outward current which is most likely carried by potassium ions. In the human urinary bladder, this effect is mediated by a glibenclamide-sensitive potassium channel, as glibenclamide is able to diminish the relaxant effect of cromakalim and to preve…
Voltage- and Agonist-Induced Activation of Smooth Muscle of the Human Upper Urinary Tract: Different Mechanisms
Smooth muscles are such a remarkably diverse group of tissues that the difference in properties between any two of them may be as great as between a smooth muscle and a striated muscle. With this diversity it is not surprising that the ways in which different stimuli initiate contraction are also extremely varied and interesting although we still know very little about the details of the mechanisms involved. In an attempt to shed some light on the cellular contraction cycle of smooth muscle of the human upper urinary tract, this article will focus on two topics: 1. Previous findings in smooth muscle research will be summarized and discussed briefly as they are pertinent to an understanding …
ACTION POTENTIAL, MEMBRANE CURRENTS AND FORCE OF CONTRACTION IN MAMMALIAN HEART MUSCLE FIBRES TREATED WITH QUINIDINE
The effects of quinidine on electrical and mechanical activity were investigated in atrial and/or ventricular heart muscle preparations from guinea pigs and cats. Quinidine (1--100 micrometer) exerted negative inotropic effects in papillary muscles from guinea pigs and cats. In guinea-pig left atria, a positive inotropic effect was superimposed on the negative inotropic effect in response to quinidine. Quinidine (100 micrometer) prolonged the duration of the action potential in guinea-pig atria but shortened it in guinea-pig ventricular muscle. In cat papillary muscles, the late repolarization was markedly prolonged by quinidine, but virtually no change of the plateau phase was observed. Th…
Effects of papaverine on human isolated bladder muscle
Papaverine is a non-specific smooth muscle relaxant and is thought to act at a site beyond the receptor sites on the cell membrane. In this study the relaxing properties of papaverine were tested in isolated muscle strips from the human bladder dome. In carbachol-induced contractions papaverine, even in high concentrations of 10(-4) mol/l had virtually no effects on peak tension generation, whereas the fading was accelerated and the steady state tension at 30 min. was reduced by about 54%. In contrast, high potassium-induced contractions were relaxed by papaverine in a concentration-dependent way; a concentration of papaverine of 10(-4) mol/l produced full relaxation. These findings might p…
Papaverine in Human Bladder Muscle
It is generally assumed that drugs which induce relaxation of smooth muscles may be of clinical importance in some urological disorders; such drugs are indeed widely used, for example, in the therapy of unstable bladders or to facilitate the passage of ureteral stones. Recently, papaverine has been shown to be very effective, e.g., in relaxing smooth muscles of the corpus cavernosum penis, thereby inducing erections in many impotent men (Virag 1982). The purpose of this study is to determine the relaxing properties of papaverine in isolated muscle strips from the human detrusor and to evaluate its potential clinical importance.
Zur Wirkung von Baralgin auf die glatte Muskulatur des menschlichen oberen Harntraktes
Pharmaka mit relaxierender Wirkung auf die glatte Muskulatur werden vielfach zur Behandlung der Hamsteinkolik und zur Beschleunigung der Hamsteinpassage verwendet. Die Wirkung solcher Spasmolytika wird im allgemeinen als neurotrop oder muskulotrop klassifiziert. Die neurotrope Wirkung wird mit einer Beeinflussung des autonomen Nervensystems in Verbindung gebracht, wahrend die muskulotrope Wirkung in einer direkten Beeinflussung der glatten Muskelzelle gesehen wird. Beispiele fur Pharmaka mit neurotroper Wirkung sind Anticholinergika oder α-Rezeptorenblocker, wahrend Papaverin eine klassische Substanz aus der Gruppe der muskulotropen Spasmolytika ist.
Stimulation of calcium uptake by norepinephrine or high external potassium in human calyces and renal pelvis.
The effects of stimulation with either 10 mumol/l norepinephrine or 85 mmol/l extracellular potassium concentration on calcium uptake were studied in muscle strips from human renal calyces and from the renal pelvis. The apparent uptake of calcium under control conditions was essentially complete after 30 min. Stimulation of the muscle strips with norepinephrine or high external potassium significantly (P less than 0.05) increased the calcium uptake over the control values at 30 and 100 min, whereas 45Ca efflux was virtually not affected. It is concluded that the mechanical responses of the muscle strips to norepinephrine or high external potassium correspond with an increased uptake of calc…
Adenosine activates a potassium conductance in guinea-pig atrial heart muscle.
Adenosine shortens the action potential and diminishes the force of contraction in guinea-pig left atria. These effects may be brought about by the activation of a potassium conductance. This assumption is supported by voltage clamp and 42K release experiments.