Effect of flavonoids of different structure on peroxidation of neutral lipids of animal origin

The effect of flavonoids of different structure (baikalein, baikalin, quercetin, dihydroquercetin, genistein, and daidzein) on the process of formation of lipid hydroperoxides during thermoinduced autooxidation of neutral lipids of animal origin. The minimum inhibitory concentration of isoflavones was found to be equal to 10(-3) M. Effective inhibitory concentration of other flavonoids (except baikalin) was equal to 10(-4) M. Baikalin was an effective promoter of lipid peroxidation. The antioxidant activity of the flavonoids tested was calculated taking ionol as a reference.     

Inhibition of Ca-transport ATPase from synaptosomal vesicles by flavonoids

The inhibitory action of the flavonoid quercetin has been examined on the calcium-transport ATPase of synaptosomal vesicles and compared to that of two other flavonoids, morin and rutin. We have found that while quercetin caused a 50% inhibition of calcium transport at a concentration of 15 μM, morin and rutin had similar effects at concentrations of about 200 μM. A similar order of potency was observed also for ATP hydrolysis, though at higher concentrations. Quercetin also strongly inhibited phosphorylation of membrane proteins by ATP in synaptosomal vesicles. Rutin and morin had an almost negligible effect on membrane protein phosphorylation. The order of inhibitory potency of the flavonoids on the Ca²⁺-transport ATPase from synaptosomal vesicles: quercetin > morin > rutin, could be linked to their possible solubility in the membrane lipid phase since: (1) it paralleled their partitioning between a mixture of oil and water; (2) it paralleled their uptake from the reaction mixture by synaptosomal vesicles and phosphatidylcholine liposomes; (3) they had almost equal potency as inhibitors of the water soluble system of histone phosphorylation by protein kinase.     

Effects of aplysiatoxin and debromoaplysiatoxin on growth and differentiation of normal human bronchial epithelial cells

The effects of aplysiatoxin and debromoaplysiatoxin on the clonal growth rate, cross-linked envelope formation and plasminogen activator secretion of normal human bronchial epithelial cells were studied. Neither compound was mitogenic over a wide range of concentrations (10^–13 to 10^–7M). Both aplysiatoxin and debromoaplysiatoxin inhibited clonal growth rate with 50% inhibitory concentrations of 3 × 10^–11M and 10^–10M, respectively. Both compounds induced the formation of cross-linked envelopes and increased plasminogen activator secretion with equal potency. These data are similar to those previously obtained with 12-0-tetradecanoylphorbol-13-acetate and teleocidin B and suggest that aplysiatoxin and debromoaplysiatoxin induce terminal squamous differentiation in normal human bronchial epithelial cells.Abbreviations TPA 12-0-tetradecanoylphorbol-13-acetate - NHBE Normal Human bronchial epithelial - ID₅₀ 50% inhibitory concentration (dose) - PA Plasminogen activator - CLE Cross-linked envelope - LHC Laboratory of Human Carcinogenesis     

Inhibition of Ca2+-transport ATPase from synaptosomal vesicles by flavonoids

The inhibitory action of the flavonoid quercetin has been examined on the calcium-transport ATPase of synaptosomal vesicles and compared to that of two other flavonoids, morin and rutin. We have found that while quercetin caused a 50% inhibition of calcium transport at a concentration of 15 μM, morin and rutin had similar effects at concentrations of about 200 μM. A similar order of potency was observed also for ATP hydrolysis, though at higher concentrations. Quercetin also strongly inhibited phosphorylation of membrane proteins by ATP in synaptosomal vesicles. Rutin and morin had an almost negligible effect on membrane protein phosphorylation. The order of inhibitory potency of the flavonoids on the Ca²⁺-transport ATPase from synaptosomal vesicles: quercetin > morin > rutin, could be linked to their possible solubility in the membrane lipid phase since: (1) it paralleled their partitioning between a mixture of oil and water; (2) it paralleled their uptake from the reaction mixture by synaptosomal vesicles and phosphatidylcholine liposomes; (3) they had almost equal potency as inhibitors of the water soluble system of histone phosphorylation by protein kinase.     

Effects of flavonoid on calcium content in femoral tissue culture and parathyroid hormone-stimulated osteoclastogenesis in bone marrow culture in vitro

The effect of various flavonoids, which are present in food and plants, on bone calcium content and osteoclastogenesis were investigated to compare action of flavonoid on bone formation and bone resorption in vitro. Rat femoral-diaphyseal (cortical bone) and -metaphyseal (trabecular bone) tissues were cultured for 48 h in Dulbecco’s modified Eagle’s medium (high glucose) supplemented with antibiotics and bovine serum albumin. Amoung quercetin, myricetin, kaempferol, isorhamnetin, curcumin, hesperidin, or astaxanthin in the range of 10⁻⁷–10⁻⁵ M, culture with quercetin (10⁻⁶ or 10⁻⁵ M) caused a significant increase in diaphyseal calcium content. Such an effect was not seen in other compounds. Mouse bone marrow cells were cultured for 7 days in the presence of parathyroid hormone (PTH; 10⁻⁷ M), a bone-resorbing factor, in vitro. Culture with PTH caused a significant increase in osteoclast-like cell formation. This increase was significantly inhibited in the presence of quercetin, myricetin, kaempferol, isorhamnetin, or curcumin in the range of 10⁻⁸–10⁻⁶ M. Such an effect was not seen in the case of hesperidin or astaxanthin. In addition, culture with PTH (10⁻⁷ M) caused a significant decrease in diaphyseal calcium content. This decrease was completely prevented in the presence of quercetin, myricetin, kaempferal, or isorhamnetin of 10⁻⁶ M. This study demonstrates that various flavonoids have a potent inhibitory effect on osteoclastogenesis and bone resorption rather than bone formation in vitro. Among various flavonoids, quercetin had a stimulatory effect on bone formation and an inhibitory effect on bone resorption in vitro.     

Endotoxin-neutralizing activity and mechanism of action of a cationic α-helical antimicrobial octadecapeptide derived from α-amylase of rice

We have previously reported that AmyI-1-18, an octadecapeptide derived from α-amylase (AmyI-1) of rice, is a novel cationic α-helical peptide that exhibited antimicrobial activity against human pathogens, including Porphyromonas gingivalis, Pseudomonas aeruginosa, Propionibacterium acnes, Streptococcus mutans, and Candida albicans. In this study, to further investigate the potential functions of AmyI-1-18, we examined its inhibitory ability against the endotoxic activities of lipopolysaccharides (LPSs, smooth and Rc types) and lipid A from Escherichia coli. AmyI-1-18 inhibited the production of endotoxin-induced nitric oxide (NO), an inflammatory mediator, in mouse macrophages (RAW264) in a concentration-dependent manner. The results of a chromogenic Limulus amebocyte lysate assay illustrated that the ability [50% effective concentration (EC₅₀): 0.17 μM] of AmyI-1-18 to neutralize lipid A was similar to its ability (EC₅₀: 0.26 μM) to neutralize LPS, suggesting that AmyI-1-18 specifically binds to the lipid A moiety of LPS. Surface plasmon resonance analysis of the interaction between AmyI-1-18 and LPS or lipid A also suggested that AmyI-1-18 directly binds to the lipid A moiety of LPS because the dissociation constant (K_D) of AmyI-1-18 with lipid A is 5.6 × 10⁻¹⁰ M, which is similar to that (4.3 × 10⁻¹⁰ M) of AmyI-1-18 with LPS. In addition, AmyI-1-18 could block the binding of LPS-binding protein to LPS, although its ability was less than that of polymyxin B. These results suggest that AmyI-1-18 expressing antimicrobial and endotoxin-neutralizing activities is useful as a safe and potent host defense peptide against pathogenic Gram-negative bacteria in many fields of healthcare.     

Inhibitory effect of regucalcin on Ca2+/calmodulin-dependent cyclic AMP phosphodiesterase activity in rat kidney cytosol

The effect of regucalcin, a novel Ca²⁺-binding protein, on Ca²⁺/ calmodulin-dependent cyclic adenosine monophosphate (AMP) phosphodiesterase activity in the cytosol of rat renal cortex was investigated. Regucalcin with physiologic concentration (10^-7 M) in rat kidney had no effect on cyclic AMP phosphodiesterase activity in the absence of CaCl₂ and calmodulin. However, the activatory effect of both CaCl₂ (10 µM) and calmodulin (20 U/ml) on cyclic AMP phosphodiesterase was markedly inhibited by the addition of regucalcin (10^-8 to 10^-6 M) in the enzyme reaction mixture. The inhibitory effect of regucalcin on the enzyme activity was also seen in the presence of CaCl₂ (5-50 µM) or calmodulin (5-50 U/ml) with increasing concentrations. The presence of trifluoperazine (10 µM), an antagonist of calmodulin, caused a partial inhibition of Ca²⁺ /calmodulin-dependent cyclic AMP phosphodiesterase activity. This inhibition was further enhanced by the addition of regucalcin (10^-7 M). The inhibitory effect of regucalcin (10^-7 M) was not seen in the presence of 20 µM trifluoperazine. Moreover, the activatory effect of calmodulin (20 U/ml) on cyclic AMP phosphodiesterase was not entirely seen, when calmodulin was added 10 min after incubation in the presence of CaCl₂ (10 µM) and regucalcin (10^-7 M). The present results demonstrates that regucalcin has an inhibitory effect on Ca²⁺ /calmodulin-dependent cyclic AMP phosphodiesterase activation in the cytosol of rat renal cortex.     

Carbon dioxide and biearbonate in cell division

Summary The effects of carbon dioxide and of bicarbonate on cell division were studied on synchronized cells of the high-temperature green alga, Chlorella 7-11-05. After 7 hours of growth in nutrient medium in light, cells were centrifuged and resuspended in distilled water or in bicarbonate and placed in darkness. Atmospheric air, or a mixture of carbon dioxide and air, was bubbled through algal suspensions during the dark period. In distilled water cells readily divided in atmospheric air but not in 1% (2.6·10^-4 M) or in higher concentrations of carbon dioxide. The suspension of cells in bicarbonate counteracted the inhibitory action of carbon dioxide. A minimum molar concentration of bicarbonate necessary to counteract the inhibitory effect of carbon dioxide was found to be equal to the molar concentration of carbon dioxide in the suspending fluid. The highest concentration of carbon dioxide, the adverse effect of which could not be balanced by any concentration of bicarbonate, was found to be in the vicinity of 1.3·10^-2 M (50% CO₂ in air). Possible effects on cell division of the change in Ph and the implicated role of carbon dioxide in normal and neoplastic growth were discussed.     

Tumor necrosis factor alpha stimulates arachidonic acid metabolism in human osteoblastic osteosarcomal cells

The effects of tumor necrosis factor alpha (TNF-α) on arachidonic acid (AA) metabolism were investigated by prelabeling the human osteoblastic osteosarcoma cell line, G292, with [³H]AA. TNF-α differentially stimulates cyclooxygenase and lipoxygenase pathways of AA metabolism in a dose response manner in the cells. The highest concentration of TNF-α (10⁻⁸ M) significantly increased the cyclooxygenase pathway, with prostaglandin E₂ (PGE₂) being a major product. However, at the lowest concentration (10⁻¹⁰ M) of TNF-α, 15-hydroxyeicosatetraenoic acid (HETE) production was significantly increased, with no significant effects on the other identifiable products. When the concentration of TNF-α was increased to 10⁻⁹ M leukotriene B₄ (LTB₄), 15-, 12-, and 5-HETE were significantly increased. The calcium ionophore A23187 (10⁻⁶ M) significantly increased 15-HETE production, without significantly affecting cyclooxygenase metabolites. However, a combination of TNF-α (10⁻⁸ M) and A23187 (10⁻⁶ M) caused an inhibitory effect on each agent-induced PGE₂ or 15-HETE production.     

Interactive effect of nitric oxide and brassinosteroids on photosynthesis and the antioxidant system of <Emphasis Type="Italic">Lycopersicon esculentum</Emphasis>

An interactive effect of nitric oxide and 24-epibrassinolide (EBL) or 28-homobrassinolide (HBL) was investigated in Lycopersicon esculentum Mill. cv. K-21. Seeds prior to sowing were exposed to sodium nitroprusside (SNP) (0, 10⁻⁵ M or 1 M), a nitric oxide donor, for 8 h, and the resulting seedlings were subsequently sprayed with 10⁻⁸ M EBL or HBL at 30-day stage. The analysis of plant samples after 24 h of the EBL or HBL spray showed that the lower SNP concentration (10⁻⁵ M) favored the growth, pigment content, photosynthetic and enzymatic activities, and also improved the antioxidant system. However, 1 M SNP had inhibitory impact on most of the indices, except the antioxidant system. Brassinosteroids (EBL or HBL), on the other hand, had a stimulatory impact on the aforementioned indices. The inhibitory effect of SNP (1 M) was neutralized by the application of BRs, where EBL was more effective than HBL.     

Modulation of Adherence and Chemotaxis of Macrophages by Norepinephrine. Influence of Ageing

We evaluated thein vitro effect of norepinephrine (NE), over the range of concentrations between 10^-12 M and 10^-3 M, on adherence (to plastic surfaces) and chemotaxis (in a Boyden chamber) of peritoneal macrophages from BALB/c mice of different ages: young (12 weeks), adult (22 weeks), mature (48 weeks) and old (72 weeks). Increased adherence was induced by 10^-12 M of NE in macrophages from young, adult, mature and old mice. Also, 10^-9 M stimulated adherence in old animals, 10^-5 M in mature mice, and 10^-3 M in both young and old mices. With respect to chemotaxis, the low concentration of NE (10^-12 M) was stimulatory only in young and adult animals, higher concentrations (10^-5 M and 10^-7 M) were inhibitory for macrophages from mature and old animals, and the highest concentration of NE (10^-3M) stimulated this capacity of macrophages only in young and mature animals. The conclusion is that while the mobility of macrophages to the focus of infection (i.e. chemotaxis) is stimulated by low concentrations of NE (10^-12, M) only in young-adult animals, this neurotransmitter induces a decline in this capacity in mature and old mice at high concentrations (10^-5 M - 10^-7 M). Also, macrophages from old animals have lost the capacity to respond to pharmacological (10^-3 M) concentrations of NE. The lower capacity of response to NE by macrophages from old animals possibly contributes to immunosenescence.     

Antioxidant,anti‐inflammatory,and enzyme inhibitory activity of natural plant flavonoids and their synthesized derivatives

The synthesized flavonoid derivatives were examined for their antioxidant, anti‐inflammatory, xanthine oxidase (XO), urease inhibitory activity, and cytotoxicity. Except few, all the flavonoids under this study showed significant antioxidant activity (45.6%–85.5%, 32.6%–70.6%, and 24.9%–65.5% inhibition by DPPH, ferric reducing/antioxidant power, and oxygen radical absorption capacity assays) with promising TNF‐α inhibitory activity (42%–73% at 10 μM) and IL‐6 inhibitory activity (54%–81% at 10 μM) compared with that of control dexamethasone. The flavonoids luteolin, apigenin, diosmetin, chrysin, O^3?, O⁷‐dihexyl diosmetin, O^4?, O⁷‐dihexyl apigenin, and O⁷‐hexyl chrysin, showed an inhibition with IC₅₀ values (4.5‐8.1 μg/mL), more than allopurinol (8.5 μg/mL) at 5 μM against XO and showing more than 50% inhibition at a final concentration (5 mM) with an IC₅₀ value of ranging from 4.8 to 7.2 (μg/mL) in comparison with the positive control thiourea (5.8 μg/mL) for urease inhibition. Thus, the flavonoid derivatives may be considered as potential antioxidant and antigout agents.     

Inhibitory effects of GABA on synaptic excitation in isolated rat hippocampal slices

In research on -aminobutyric acid (GABA) used at different concentrations on the amplitude of EPSP within populations (PEPSP), as recorded from dentrites in isolated hippocampal slices, GABA induced a dose-dependent reversible reduction in PEPSP amplitude with no noticeable signs of desensitization. Highest sensitivity to GABA was shown by PEPSP in hippocampal zone CA1 (threshold concentration: 3×10^–5–2×10^–4 M; (concentration at which the effect equal to 1/2 of maximum occurs) IC₅₀: 5×10^–4–1×10^–3 M). The effects of GABA on PEPSP were not blocked by bicuculline, picrotoxin, or penicillin. Action of GABA on dendritic antidromic population spike (DAPS — postynaptic effects) were slightly diminished by these blockers. Baclofen inhibited PEPSP more powerfully than GABA (threshold concentration: 1×10^–6 M: IC₅₀: 3×10^–6 M), although it only produced a minor reduction in DAPS amplitude even at high concentrations. It is concluded that the inhibitory effect of GABA on PEPSP in hippocampal zone CA1 may be put down mainly to its presynaptic action mediated by GABA_B receptors on axonal terminals of Schaffer collaterals.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 5, pp. 627–633, September–October, 1990.     

Arsenite as an Inducer of Lipid Peroxidation in Saccharomyces cerevisiae Cells

The ability of sodium arsenite at concentrations of 10^–2, 10^–4, and 10^–6 M to induce lipid peroxidation in Saccharomyces cerevisiae cells was studied. Arsenite at the concentrations 10^–2 and 10^–4 M enhanced lipid peroxidation and inhibited the growth of yeast cells. Enhanced lipid peroxidation likely induced oxidative damage to various cellular structures, which led to suppression of the metabolic activity of cells. Arsenite at the concentration 10^–6 M did not activate lipid peroxidation in cells. All of the tested arsenite concentrations inhibited the activity of -ketoglutarate dehydrogenase and pyruvate dehydrogenase in cells. The inference is made that the toxicity of arsenite may be related to its stimulating effect on intracellular lipid peroxidation.     

Melatonin Effects on Steroid Production by Rainbow Trout Ovarian Follicles In Vitro: Influence of Stage of Follicle Maturation

Rainbow trout ovarian follicles at four different stages of maturation (very early vitellogenesis, early vitellogenesis, peak vitellogenesis, and pre-ovulatory) were incubated either in Cortland's medium alone, or medium containing melatonin at one of five concentrations (1 × 10^-10, 1 × 10^-8, 1 × 10^-6, 1 × 10^-4 or 1 × 10^-2M) to assess the direct actions of melatonin on basal (non-gonadotrophin stimulated) secretion of 17β-estradiol and testosterone. Testosterone secretion by peak vitellogenic phase follicles was significantly (p &lt; 0.01) reduced by melatonin at 1 × 10^-4 or 1 × 10^-2 M, but there were no other significant effects of melatonin on T secretion. There were no significant effects of melatonin at concentrations of 1 × 10^-10 or 1 × 10^-8 M on 17β-estradiol secretion for any stage of follicular maturation, although for follicles at the peak vitellogenesis stage, melatonin at 1 × 10^-6 M had a significant (p &lt; 0.05) stimulatory effect compared with the controls. Melatonin also stimulated 17β-estradiol secretion by very early vitellogenic stage follicles (1 × 10^-2 M concentration; p &lt; 0.05). At concentrations of 1 × 10^-4 and 1 × 10^-2 M, melatonin significantly (p &lt; 0.01) inhibited 17β-estradiol secretion of peak vitellogenic and preovulatory stage follicles. The findings suggest a stimulatory action of melatonin on steroidogenesis of early stage ovarian follicles, a shift to an inhibitory action of the higher concentrations of melatonin in later stages of development, but with a bimodal action of melatonin (related to hormone concentration) being present during the time of maximum follicular growth.     

Effect of phosphocreatine on reflex activity of the brain stem reticular formation

The effects of phosphocreatine (PCr) on startle reflexes, known to be relayed through the brain stem reticular formation (RF), were investigated on chloralose-anesthetized rats. PCr (10^–6 to 10^–3 M) was either applied superficially to the bottom of the fourth ventricle or microinjected into the reticular gigantocellular nucleus. The PCr effect was found to depend on its concentration. At low concentrations (10^–6 to 10^–5 M), PCr markedly facilitated the reflexes; sometimes its application gave rise to additional, later and longer, discharges following startle reflexes, whereas an inhibitory effect predominated at higher PCr concentration (10^–4 to 10^–3 M). Possible mechanisms of PCr action on the studied reflexes are discussed.Neirofiziologiya/Neurophysiology, Vol. 25, No. 3, pp. 272–278, 1993.     

Bidirectional effect of met-enkephalin on macrophage effector functions

Summary Met-enkephalin (ME) exerts a bimodal effect on functional activities of rat peritoneal macrophages (PM); in a range of low concentration (10^-9-10^-7 M) antibody dependent cellular cytotoxicity (ADCC)was markedly stimulated with a simultaneous decrease of Fc receptor (FcR) mediated phagocytosis while the opposite was observed at 10^-6-10^-5 M concentrations.Studying the possible underlying mechanism(s) the followings were recorded: (1) ME in all applied concentrations induced an early Na⁺ influx which was followed by a Ca²⁺ efflux in the range of low concentrations. In the range of high concentrations Na⁺ influx was accompanied by a Ca²⁺ influx. (2) ME at 10^-8 M concentration induced a rise in cGMP level with a plateau in the 60–120th min of incubation. This effect was prevented by 10^-5 M of naloxone. At 10^-6 M concentration a transient rise of cAMP level was recorded which was not affected by naloxone. (3) Verapamil in 10^-6 M abolished both the Ca²⁺ influx and the rise in cAMP level induced by 10^-6-10^-5 M ME but not the rise in cGMP level induced by lower ME concentrations. (4) cAMP elevation by high ME concentrations was abolished by enkephalinase inhibitory puromycin. (5) PM-enkephalinase as assessed by the cleavage of fluorogenic substrate L-alanine beta naphthylamide (ABNA), was inhibited by 10^-6-10^-5 M of ME. This inhibition was abolished by verapamil, but not affected by naloxone. In the range of low concentrations ME appears to act on specific delta opioid receptors and its action is positively coupled to guanylate cyclase. In relatively higher concentrations ME-action is not mediated by specific delta opioid receptors and it appears to involve Ca²⁺ influx, adenylate cyclase activation as well as the processing of hormone by PM-enkephalinase.     

The effects of abscisic acid and methyl jasmonate on 1-aminocyclopropane 1-carboxylic acid conversion to ethylene in hypocotyl segments of sunflower seedlings,and their control by calcium and calmodulin

The conversion of 1-aminocyclopropane 1-carboxylic acid (ACC) to ethylene by hypocotyl segments of sunflower (Helianthus annuus L.) seedlings was inhibited by abscisic acid (ABA) and methyl jasmonate (Me-Ja), and this inhibitory effect increased with increasing concentration of both growth regulators. On the contrary, CaCl, enhanced ACC conversion to ethylene at the concentrations of 10^-4 M and 5 x 10^-4 M, however lower and higher concentrations had no significant action. CaCl, (5 x 10^-4M) seemed to magnify the inhibition of the reaction induced by ABA, whereas it reduced (5 x 10^-4M) and even abolished (10^-3M) the inhibitory action of Me-Ja. The results obtained with a Ca²⁺ chelator (EGTA), a Ca²⁺ channel blocker (nifedipine) and calmodulin antagonists (W7 and TFP), given in association with ABA or Me-Ja, suggested that calcium was involved in the inhibition of ACC conversion to ethylene by ABA and Me-Ja through an interaction with calmodulin. However, the mechanism of action of the two growth regulators seemed to be different, since all treatments which resulted in a decrease in cytosolic Ca²⁺ concentration or in calmodulin action induced a decrease in the effect of ABA and an increase in the effect of Me-Ja.Abbreviations ABA abscisic acid - ACC 1-aminocyclopropane 1-carboxylic acid - EFE ethylene for enzyme - EGTA ethylene glycol-bis-2-aminoethyl tetraacetic acid - Me-Ja methyl jasmonate - NIF nifedipine - TFP trifluoperazine dihydrochloride - W7 N-(6-aminohexyl)5-chloro-l-naphthalenesulfonamide hydrochloride     

The effect of indol-3-yllactic acid on maize seedling growth

D,L-indol-3-yllactie acid was applied at concentrations 0.2 – 20 mg 1^-1 (10^-6–10^-4M) to the roots of 3-d-old intact maize seedlings grown in the dark and in the light. By day 3 after application, ILA at lower concentrations (0.2–1 mg l^-1) caused slight increase in the mass of etiolated plants, mainly roots. Shoot and root length was not increased. ILA at concentrations equal to, or greater than, 2 mg 1^-1 reduced the length of the main roots and from 10 mg 1^-1 on also the length of the shoots. In contrast, root mass was decreased by higher ILA concentrations to a lesser extent than shoot mass. The response to ILA application of etiolated seedlings differed from that of the seedlings grown in the light only at 20 mg 1^-1. The inhibitory effect was more pronounced in the case of quickly growing etiolated plants.     

Testing of Neurotropic Effects of Viagra

Using intracellular recording, we studied electrical activity of unidentified neurons of the Helix visceral ganglion under conditions of application of Viagra (sildenafil citrate). Neurotropic effects of Viagra were clearly pronounced at concentrations of 10^-5 and 10^-4 M; they were excitatory and reversible. In the case where the concentration was 10^-3 M, the effect of Viagra was converted into an inhibitory one; some hyperpolarization of the neuronal membrane, a decrease in the amplitude of action potentials (APs), and reduction of their first derivatives reflecting the rates of rise of integral inward and outward currents were observed. In the concentration of 0.5 × 10^-2 M (5.0 mM), Viagra evoked hyperpolarization of the neuronal membrane by 8 to 10 mV. Against the background of such hyperpolarization, APs were rather rapidly reduced and disappeared; after washing out from the preparation tested, the initial values did not recover. The obtained data allow us to believe that the uncontrolled and excessive use of Viagra can be rather dangerous since it can lead to noticeable functional disturbances in the nervous system.