Lithium fluxes in Paramecium and their relationship to chemoresponse.

Paramecia respond to environmental stimuli by altering swimming behavior to disperse from or accumulate in the vicinity of the stimulus. We have found, using the T-maze assay, that treatment of paramecia with LiCl in a time- and concentration-dependent manner modifies the normal response to folate, acetate, and lactate from attraction to no response or even repulsion. Responses to NH4Cl were unaffected and to cAMP were variably affected by LiCl. Cells incubated in the presence of K+, or both Na+ and K+, but not Na+ alone reliably recovered attraction to folate. Treatment of cells with 4 mM LiCl for 1 h dramatically slowed swimming speed from about 1 mm/s in NaCl or KCl (control) to 0.18 mm/s in LiCl. Li-treated cells subsequently incubated in 4 mM NaCl, KCl or sequentially in KCl and NaCl for a total of 20 min increased their swimming speed to 0.35, 0.45 and 0.67 mm/s, respectively. Paramecia readily took up Li+ in Na(+)- and K(+)-free media reaching intracellular concentrations of 5-10 mM in 10 mM extracellular Li+. Efflux of intracellular Li+ was stimulated 35% by extracellular 10 mM NaCl and 185% by 10 mM KCl over 10 mM choline chloride. Incubation of cells in 10 mM LiCl for 1 h inhibited the rate of Ca2+ efflux by 44% compared to cells in 10 mM NaCl. This may relate to the mechanism by which Li+ perturbs chemoresponse. A mutant with defects in Ca homeostasis responds normally to NH4Cl, but not to any of the stimuli that are affected by LiCl.     

Crystallization of phosphatidylserine bilayers induced by lithium

Utilizing differential scanning calorimetry and x-ray diffraction, 1,2-dimyristoyl-L-glycero-3-phospho-L-serine (DMPS) was shown to form hydrated bilayer membrane structures exhibiting a gel leads to liquid crystalline transition at 39 degrees C (delta H = 7.2 kcal/mol). Addition of up to molar concentrations of the alkali halides NaCl, KCl, Rl Cl, and CsCl produced relatively minor changes in DMPS bilayer structure or stability. For example, in the presence of 0.5 M NaCl, the transition temperature (Tc = 42 degrees C) and transition enthalpy (delta H = 7.0 kcal/mol) show only minor changes. In marked contrast, addition of LiCl results in "'crystallization" of the DMPS bilayer membrane structure. At 0.5 M LiCl, the crystalline DMPS exhibits a bilayer gel leads to liquid crystal transition at 89 degrees C accompanied by a high enthalpy change, delta H = 16.0 kcal/mol. Thus, Li+ induces an isothermal crystallization of DMPS bilayers, the hydrocarbon chains adopting a more ordered packing mode than the "hexagonal" arrangement of the gel state. In view of the widespread use of lithium in the treatment of manic-depressive illness, we also raise the possibility that interaction of Li+ with anionic membrane phospholipids could play a role in its pharmacological action.     

Lithium inhibits amplification or action of the maturation-promoting factor (MPF) in meiotic maturation of starfish oocytes

Microinjection of LiCl reversibly inhibits hormone-induced meiotic maturation of starfish oocytes. Microinjection of NaCl (even in ouabain-treated oocytes) or KCl, or external application of LiCl have no such effect. Blockade of meiotic maturation by Li+ occurs even when microinjection is performed after the hormone dependent period has ended, that is the period during which the hormone must be present in the medium in order that meiosis can take place. Li+ microinjection prevents oocytes from meiosis reinitiation following transfer of cytoplasm taken from maturing oocytes, which contain a maturation-promoting factor (MPF). Cytoplasm taken from Li+-injected and hormone-treated oocytes does not trigger meiosis reinitiation when transferred in control immature oocytes. Intracellular pH does not change following LiCl microinjection. Simultaneous microinjection of either K+, Na+, or EGTA does not prevent Li+-dependent inhibition in oocytes.     

The modifications of the final stages of the complement reaction by alkali metal cations.

We studied the effects of alkali metal cations on the terminal stages of complement lysis of human and sheep HK erythrocytes. Sensitized erythrocytes (EA) were reacted with limited amounts of complement for 1 hr at 37 degrees C in buffer containing 147 mM NaCl (Na buffer), which resulted in 10-40% lysis. The unlysed cells were washed with Na buffer at 0-2 degrees C and incubated for 1 hr at 37 degrees C in buffers containing 147 mM of the various alkali metal cations. Although additional lysis (25 to 65%) occurred with K, Rb, or Cs buffer, only minor degrees developed with Na or Li buffer, only minor degrees developed with Na or Li buffer. Intermediate levels occurred with 100 mM of the divalent alkali cations. Halogen ions and SCN-(147 MM), Ca++ (0.15mM), and Mg++ (0.5 mM) did not alter the effect of the alkali metal cations. Lysis occurring in K+, Rb+ or Cs+ proceeded without lag, was temperature dependent with an optimum of 43 degrees C, and had a pH optimum of 6.5. Lysis in K and Na buffers was unaffected by 10(-3) to 10(-5) M ouabain. Experiments with mixtures of cations indicated that Na+ had a mild inhibitory effect that could be totally overcome by K+, partially by Rb+, and not at all by Cs+. Li+ had a strong inhibitory effect, 6 X 10(-5) M causing 50% inhibition in buffers containing 147 mM K+, Rb+, or Cs+. By using intermediate complexes of EA and purified complement components we demonstrated that K+ enhances the lytic action of C8 on EAC1-7 as well as that of C9 on EAC1-8. It was known that Li+ facilitates lysis when acting on the entire complement reaction. We found that Li+ enhanced the lytic action of C8 on EAC1-7, with a kinetic that differed from that of the K+ effect. In addition, Li+ inhibited the enhancing effect of K+ upon lysis of EAC1-8 by C9. This occurred at concentration of Li+ similar to those which inhibited the additional lysis by K+, Rb+, and Cs+ of cells that were pretreated in Na buffer with the entire complement sequence. We propose that the major effects of alkali metal cations on complement lysis are due to their interaction with C8 and/or membrane constitutes.     

Primary structure and characteristics of the melibiose carrier of Klebsiella pneumoniae.

The melB gene coding for the melibiose carrier of Klebsiella pneumoniae was cloned and sequenced. There were two potential translation initiation sites. It was predicted that the melibiose carrier consists of 471 (or 467) amino acid residues. Seventy-eight percent of the 471 amino acids were identical to the Escherichia coli melibiose carrier. Sugar transport characteristics were studied using an E. coli mel- mutant expressing cloned K. pneumoniae melB gene. Accumulation of melibiose via the K. pneumoniae melibiose carrier was not stimulated by adding NaCl or LiCl which stimulates melibiose accumulation via the E. coli melibiose carrier. Lactose was accumulated only in the presence of LiCl. TMG (methyl-1-thio-beta-D-galactopyranoside) was accumulated in the absence of added NaCl or LiCl. The accumulation was stimulated by LiCl but not by NaCl. Rapid H+ uptake was observed when melibiose or TMG was added to cell suspensions. These results suggest that the preferred cation couplings via K. pneumoniae melibiose carrier are H(+)-melibiose, Li(+)-lactose, and H+/Li(+)-TMG. This coupling spectrum is quite different from that of the E. coli melibiose carrier. It is of special interest that the K. pneumoniae melibiose carrier seems to be lacking the ability to recognize Na+ which is a preferred coupling cation of the E. coli melibiose carrier for all known sugar substrates. Further investigation of these two carriers may give us insight into the Na+ recognition site.     

Activation and stabilization of diaphragm-associated acetylcholinesterase by monovalent (Na+, Li+) cations

Acetylcholinesterase (AChE) activity was determined at varied pH values between 6 and 11 in rat homogenated diaphragm and in eel E. electricus soluble AChE, in the presence or absence of 115 mM NaCl or LiCl. It was observed that by using homogenated diaphragm Li+ stimulated AChE at physiological pH (7-7.4). In control (no cations) a pH "optimum" of 8.6-9 was found, while in presence of NaCl or LiCl "optima" of 9.5 and 10.2 were observed respectively. At optimum pH, AChE activity was about 2 times higher with NaCl, while with LiCl 5 times higher than the control. Preincubation of the enzyme or the homogenate in cations presence at pH 5.5 or pH 12.8 had no effect on the activity, when it was measured at pH "optima". However, without cations only 76% of the activity in optimum pH after preincubation at pH 5.5 was found. These results suggest that: (a) Li+ may neutralize negative charges of AChE more successfully than Na+, resulting in better enzyme activation and stabilization; (b) a possible enzyme desensitization induced by pH changes can be avoided by increasing Na+ concentrations and especially Li+.     

Growth of heat-injured Vibrio parahaemolyticus in media supplemented with various cations.

Mid- to late logarithmic growth phase cells of Vibrio parahaemolyticus grown in tryptic soy broth (TSB) containing 0.5, 3.0, and 7.5% NaCl were heated for 8 min at 45 degrees C in 0.1 M phosphate buffer (pH 7.2) containing 3% NaCl. Colony formation on thiosulfate-citrate-bile salts-sucrose agar (TCBS) containing 2% NaCl was greatest for unheated cells that had been grown in 7.5% NaCl-TSB; cells grown in 0.5% NaCl-TSB formed a greater number of colonies on 1.0% NaCl-TCBS. Thermal injury was evident in heated cells, regardless of the NaCl concentration in TSB growth medium. The effects of Mg2+, K+, and Li+ added as chlorides to 0.5% NaCl-TSB on the growth of nonheated and heated V. parahaemolyticus were studied. Lower levels of Mg2+ and slightly higher levels of K+ were required to replace Na+ in TSB inoculated with thermally injured cells that had been originally grown in 3.0 and 7.5% NaCl-TSB. LiCl had an inhibitory effect on both nonheated and heated cells when present in the recovery medium (0.5% NaCl-TSB) at concentrations as low as 0.5%. Increased numbers of colonies were formed by heated cells plated in MgCl2-supplemented TCBS, regardless of the NaCl concentration in the original growth medium. Potassium had little, if any, effect on colony formation by nonheated V. parahaemolyticus recovered on TCBS and may have had a detrimental effect on heat-injured cells.     

Lithium inhibits the cytolytic glucocorticoid effect on S49 mouse lymphoma cells

Cytolysis is the end point of receptor-mediated effects of glucocorticoids on S49 mouse lymphoma cells of wild-type. In the presence of 5 mM LiCl this effect of triamcinolone or dexamethasone was markedly delayed. The cytoprotective effect of Li+ against 10(-7) M triamcinolone acetonide was already manifest after 24 h of steroid incubation, and on the fifth day 50-fold more Li+-treated than control cells were viable. This effect of Li+ was not exerted through changes of the doubling time of the cells, and thus could not be ascribed to an overall reduction of protein- or RNA synthesis. Data on accumulation and effect of cyclic AMP indicated that the cytoprotective effect was independent on cyclic AMP. Furthermore Li+ did not affect the amount or affinity of glucocorticoid receptors in intact cells. By use of aqueous 2-phase partitioning and DNA-Sepharose binding of [3H]triamcinolone acetonide labelled cytosols we demonstrate that Li+ inhibits the in vitro salt-activation of the glucocorticoid-receptor complexes by 60-100%. The nuclear bound fraction of hormone-receptor complexes in intact cells at 37 degrees C was not affected by Li+. The data suggest that Li+ inhibits the cytolytic glucocorticoid effect by interacting with the hormone-receptor complexes.     

Action of botulinum A toxin and tetanus toxin on synaptic transmission

Intracellular recordings of the spontaneous activity from mammalian spinal cord neurons in culture demonstrated different sensitivities of excitatory and inhibitory synaptic transmission for the action of tetanus toxin (Tetx) and botulinum toxin type A (Botx). The effects of Tetx and Botx on spontaneous and nerve-evoked transmitter release were compared under identical experimental conditions in experiments on in vitro poisoned mouse diaphragms. At 37 degrees C completely paralyzed endplates are characterized by a very low frequency of spontaneous miniature endplate potentials (m.e.p.p.s) and by a 100% failure to evoke endplate potentials (e.p.p.s) in response to single nerve stimuli. Striking differences in the action of both toxins have been observed when the very low transmitter release probabilities of paralyzed nerve-muscle preparations were increased by tetanic nerve stimulation and/or application of potent K+-channel blockers and/or by reduction of temperature to 25 degrees C. While Botx did not change the short latency between nerve impulse and postsynaptic response, Tetx produced a temporal dispersion of the quantal release suggesting that the toxins act at different sites in the chain of events that result in transmitter release. To find further evidence to support the different actions of the toxins the spontaneous transmitter release was studied in more detail. Tetx blocked preferentially the release of so-called large mode m.e.p.p.s without affecting the frequency of the small mode ones. In contrast, Botx strongly inhibited both the small and large mode m.e.p.p.s.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of lithium-induced enzyme release from human polymorphonuclear leukocytes

Lysozyme release from purified human polymorphonuclear leukocytes was found to be uniquely enhanced by 2.5-20 mM LiCl. This effect was dose dependent and was not detected when the media was supplemented with NaCl, KCl, MgCl2, or CaCl2. The purified isotopes of Li+, 6Li, and 7Li were equally effective in enhancing lysozyme release from the cells at 10 and 20 mM, but 6Li was more effective than 7Li at 5 mM. The enhancement of enzyme release in the presence of Li+ was comparable to the enhancement observed in the presence of N-formylmethionylleucylphenylalanine (fMLP). Addition of LiCl plus fMLP did not result in lysozyme release in excess of each stimulant alone, except when the cells were incubated with 20 mM 6Li + 10(-5) M fMLP. In addition, enzyme release induced by these two agents could be further enhanced to the same degree by addition of cytochalasin D to the incubation mixtures. While similarities between enzyme release induced by LiCl and fMLP were detected, optimal stimulation of enzyme release by Li+ was much more sensitive to inhibition by pertussis toxin than was maximal fMLP stimulation. Therefore, the intracellular events altered by Li+ and the peptide may share some metabolic steps, but they differ in their sensitivity to alterations in cAMP metabolism.     

Activation by lithium ions of the inside sodium sites in (Na+ + K+)-ATPase.

1. Purified pig kidney ATPase was incubated in 30--160 mM Tris-HCl with various monovalent cations. 130 mM LiCl stimulated a ouabain-sensitive ATP hydrolysis (about 5% of the maximal (Na+ + K) activity), whereas 160 mM Tris-HCl did not stimulate hydrolysis. Similar results were obtained with human red blood cell broken membranes. 2. In the absence of Na+ and with 130 mM LiCl, the ATPase activity as a function of KCl concentration showed an initial slight inhibition (50 micrometer KCl) followed by an activation (maximal at 0.2 mM KCl) and a further inhibition, which was total at mM KCl. In the absence of LiCl, the rate of hydrolysis was not affected by any of the KCl concentrations investigated. 3. The lithium-activation curve for ATPase activity in the absence of both Na+ and K+ had sigmoid characteristics. It also showed a marked dependence on the total LiCl + Tris-HCl concentration, being inhibited at high concentrations. This inhibition was more noticeable at low LiCl concentrations. 4. In the absence of Na+, 130 mM Li+ showed promoted phosphorylation of ATPase from 1 to 3 mM ATP in the presence of Mg2+. In enzyme treated with N-ethylmaleimide, the levels of phosphorylation in Li+-containing solutions, amounted to 40% of those in Na+- and up to 7 times of those in K+-containing solutions. 5. The total (Na+ + K+)-ATPase activity was markedly inhibited at high buffer concentrations (Tris-HCl, Imidazole-HCl and tetramethylammonium-HEPES gave similar results) in cases when either the concentration of Na+ or K+ (or both) was below saturation. On the other hand, the maximal (Na+ + K+)-ATPase activity was not affected (or very slightly) by the buffer concentration. 6. Under standard conditions (Tris-HCl + NaCl = 160 mM) the Na+-activation curve of Na+-ATPase had a steep rise between 0 and 2.5 mM, a fall between 2.5 and 20 mM and a further increase between 20 and 130 mM. With 30 mM Tris-HCl, the curve rose more steeply, inhibition was noticeable at 2.5 mM Na+ and was completed at 5 mM Na+. With Tris-HCl + NaCl = 280 mM, the amount of activation decreased and inhibition at intermediate Na+ concentrations was not detected.     

Effect of prostaglandins E1 and F2 alpha on neuromuscular transmission in the frog sartorius muscle.

End plate potentials (e.p.p.s.) and miniature end plate potentials (m.e.p.p.s.) were recorded intracellularly at the neuromuscular junction of the frog sartorius muscle. Addition of as little as 8.5 x10(-8)M PGE1 reduced the mean m.e.p.p. frequency. The mean amplitude of m.e.p.p.s was not changed, the mean amplitude of the e.p.p.s and the quantum content of the transmitter released by a nerve impulse was slightly reduced. A decrease in mean m.e.p.p. frequency was also seen in response to the administration of 8.5 x 10(-8)M PG2 alpha. The mean amplitude of e.p.p.s and m.e.p.p.s and the quantum content remained unchanged. The possible presynaptic mode of action of PGs in the preparation of discussed.     

Inhibition of Na+-H+ exchange by N,N'-dicyclohexylcarbodiimide in isolated rat renal brush border membrane vesicles

The inactivation of rat renal brush border membrane Na+-H+ exchange by the covalent carboxylate reagent N,N'-dicyclohexylcarbodiimide (DCCD) was studied by measuring 1 mM Na+ influx in the presence of a pH gradient (pHi = 5.5; pHo = 7.5) and H+ influx in the presence of a Na+ or Li+ gradient ([Na+]i = 150 mM; [Na+]o = 1.5 mM). In the presence of DCCD, the rate of Na+ uptake decreased exponentially with time and transport inhibition was irreversible. At all DCCD concentrations the loss of activity was described by a single exponential, consistent with one critical DCCD-reactive residue within the Na+-H+ exchanger. Among several carbodiimides the most hydrophobic carbodiimide, DCCD, was also the most effective inhibitor of Na+-H+ exchange. With 40 nmol of DCCD/mg of protein, at 20 degrees C for 30 min, 75% of the amiloride-sensitive 1 mM Na+ uptake was inhibited. Neither the equilibrium Na+ content nor the amiloride-insensitive Na+ uptake was significantly altered by the treatment. The Na+-dependent H+ flux, measured by the change in acridine orange absorbance, was also decreased 80% by the same DCCD treatment. If 150 mM NaCl, 150 mM LiCl, or 1 mM amiloride was present during incubation of the brush border membranes with 40 nmol of DCCD/mg of protein, then Li+-dependent H+ flux was protected 50, 100, or 100%, respectively, compared to membranes treated with DCCD in the absence of Na+-H+ exchanger substrates. The combination of DCCD and an exogenous nucleophile, e.g. ethylenediamine and glycine methyl ester, increased Na+-dependent H+ flux in the presence of 80 nmol of DCCD/mg of protein, compared to the transport after DCCD treatment alone. These findings suggest that the Na+-H+ exchanger contains a single carboxylate residue in a hydrophobic region of the protein, and the carboxylate and/or a nearby endogenous nucleophilic group is critical for exchange activity.     

Effect of competing self-structure on triplex formation with purine-rich oligodeoxynucleotides containing GA repeats.

Competition between triplex formation with double-stranded DNA and oligonucleotide self-association was investigated in 23mer GA and GT oligonucleotides containing d(GA)5 or d(GT)5 repeats. Whereas triplex formation with GT oligonucleotides was diminished when temperature increased from 4 to 37 degrees C, triplex formation with GA oligonucleotides was enhanced when temperature increased within the same range due to the presence of competing intermolecular GA oligonucleotide self-structure. This self-structure was determined to be a homoduplex stabilized by the internal GA repeats. UV spectroscopy of these homoduplexes demonstrated a single sharp transition with rapid kinetics (Tm = 38.5-43.5 degrees C over strand concentrations of 0.5-4 microM, respectively, with transition enthalpy, delta H = -89 +/- 7 kcal/mol) in 10 mM MgCl2, 100 mM NaCl, pH 7.0. Homoduplex formation was strongly stabilized by multivalent cations (spermine > Mg2+ = Ca2+) and destabilized by low concentrations of monovalent cations (K+ = Li+ = Na+) in the presence of divalent cations. However, unlike GA or GT oligonucleotide-containing triplexes, the homoduplex formed even in the absence of multivalent cations, stabilized by only moderate concentrations of monovalent cations (Li+ > Na+ > K+). Through the development of multiple equilibrium states and the resulting depletion of free oligonucleotide, it was found that the presence of competing self-structure could decrease triplex formation under a variety of experimental conditions.     

Post-tetanic potentiation of miniature end-plate potential frequency at neuromuscular junction of the rat soleus muscle

1. Changes in miniature end-plate potential (m.e.p.p.) frequency by repetitive nerve stimulation were examined in the rat soleus muscle. 2. The increase of m.e.p.p. frequency was induced by repetitive stimulation and persisted for several minutes after the tetanus. That is, post-tetanic potentiation (PTP) of neuromuscular transmission was first demonstrated here in the rat soleus muscle. 3. The time course of the decay of m.e.p.p. frequency after the tetanus showed a double exponential curve which consisted of a fast decaying component (augmentation) and a slow decaying component (potentiation). 4. The magnitude of PTP depended on the stimulation frequency and its duration. It increased with the increase of duration and was at its maximum at a frequency of 100 Hz. 5. No PTP was elicited by repetitive stimulation under conditions in which end-plate potential (e.p.p.) was completely suppressed, and, moreover, m.e.p.p. frequency tended to decrease after the tetanus.     

Changes in the cooperativity of diaphragm-associated acetylcholinesterase induced by monovalent (Na+, Li+) cations

Acetylcholinesterase (AChE) activity has been determined using homogenized rat diaphragm and soluble AChE from the eel Electrophorus electricus, using as a substrate different amounts of acetylthiocholine in the presence or absence of 115 mM NaCl or LiCl. With LiCl the KM values derived from Lineweaver-Burk plots are found to be 470-650 and 1045-1425 microM without cations or with NaCl. The cooperativity of the enzyme is increased when cations are added to the homogenate, as demonstrated by changes of the Hill coefficient. With soluble AChE, only Li+ is able to produce this effect. Preincubation of the soluble enzyme at low pH (5.5) and a change to a higher value (8.7-9.4) causes a decrease of the Hill coefficient with Li+ only; this effect is not detected using the homogenate. Our results suggest the following. (i) Li+ may neutralize negative charges of AChE more successfully than does Na+, resulting in higher activity, stabilization, and cooperativity of the enzyme. (ii) The KM values calculated at high substrate concentrations (greater than 200 microM) indicate that the substrate affinity of AChE can be increased only by Li+ binding on the enzyme. (iii) Changes in pH can modulate the cooperativity and may denature allosteric sites on the enzyme that bind Li+. (iv) Membrane, cations and (or) cellular factor(s) may regulate the cooperativity and substrate affinity of AChE, when they have been affected by pH changes.     

Distinct effects of Na+ and Li+ on the induction of morphological changes in A431 cells mediated by epidermal growth factor

Epidermal growth factor (EGF) induced the formation of thin sheetlike extensions (lamellipodia) and filamentous extensions at the edges of colonies of A431 cells. To determine the necessary processes for the induction of the morphological changes mediated by EGF, the effects of a variety of ions on these changes were examined. In a NaCl solution supplemented with CaCl2, MgCl2 and glucose, no EGF-induced morphological changes were observed. However, when the NaCl was replaced with LiCl, fingerlike extensions were formed, but sheetlike extensions were not. Addition of vanadate to the NaCl solution also induced fingerlike extensions in cells treated with EGF. In contrast, sheetlike lamellipodia were formed in EGF-treated cells by the addition of K+ or PO4(3-) to the NaCl solution or by the addition of PO4(3-) to the LiCl solution. These findings indicate that Li+, K+, PO4(3-) and vanadate are involved in the processes of EGF-induced morphological changes. Since vanadate and Li+ have been shown to inhibit phosphatases, an EGF-dependent phosphorylation step may play an important role in the induction of the morphological changes observed.     

The action of ionophores at the frog neuromuscular junction

The ionophores A23187 and X537A have markedly different actions on the MEPP frequency recorded at the frog neuromuscular junction. A23187 has no significant effect at 9–17°C, but causes a small increase in MEPP frequency at 6°C. At 25°C, on the other hand, A23187 causes a marked and progressive rise in MEPP rate. It is suggested that, in spite of increased Ca²⁺ influx associated with application of the ionophore, the presynaptic terminals can maintain [Ca²⁺]_i constant at 9–17°C, although [Ca²⁺]_i rises at higher and lower temperatures, causing an increase in frequency of MEPPs. As previously reported by Kita and Van der Kloot (5) X537A causes a dramatic increase in MEPP frequency, but it is suggested that its action is more complex and probably involves an increase in Na⁺ permeability.     

Effects of glycyrrhetic acid on transmitter secretion

The investigation of the effects of glycyrrhetic acid on spontaneous secretion of transmitter from neurotermination of the frog neuromuscular synapses showed that this substance, unlike glycyrrhizic acid, increased the frequency and amplitude of m. e. p. p. in a dose-dependent manner. The effect of glycyrrhetic acid is observed in calcium-free solution which may indicate ability of glycyrrhetic acid to mobilize calcium from inner cell pools. The effects of glycyrrhetic acid, in particular increasing the frequency of the m. e. p. p., testify that glycyrrhetic acid acts on the level of presynaptic membrane.