Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.Purinergic P2 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.Receptors, Purinergic P2: A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.Pyridoxal Phosphate: This is the active form of VITAMIN B 6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (PYRIDOXAMINE).Uridine Triphosphate: Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Receptors, Purinergic: Cell surface proteins that bind PURINES with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized classes of purinergic receptors in mammals are the P1 receptors, which prefer ADENOSINE, and the P2 receptors, which prefer ATP or ADP.Purinergic Antagonists: Drugs that bind to and block the activation of PURINERGIC RECEPTORS.Purinergic P2 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P2 RECEPTORS.Receptors, Purinergic P2X: A subclass of purinergic P2 receptors that signal by means of a ligand-gated ion channel. They are comprised of three P2X subunits which can be identical (homotrimeric form) or dissimilar (heterotrimeric form).Purinergic P2X Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2X RECEPTORS. Included under this heading are antagonists for specific P2X receptor subtypes.

*  Questions Answered by Dr. Naviaux | Page 6 | Phoenix Rising ME / CFS Forums
Does anyone know what the next steps would be to be able to test suramin in a human ME/CFS trial or how far we are from that? ... Any Suramin for CDR Theory would be low dose. Tha'ts what Naviaux used in his autism trial.. Also, I thought Suramin was given ... Any Suramin for CDR Theory would be low dose. Tha'ts what Naviaux used in his autism trial.. Also, I thought Suramin was given ... I found some sources to buy Suramin but they are expensive and I have very tight budget. The cheapest suramin I have found so ...
  http://forums.phoenixrising.me/index.php?threads/questions-answered-by-dr-naviaux.54318/page-6
*  Heparin and other polyanions uncouple α1-adrenoceptors from G-proteins | Biochemical Journal
causing 50% of maximal effect (EC50) = 0.5 microM], Trypan Blue (EC50 7.1 microM) or suramin (EC50 2.1 microM) prevented ...
  http://www.biochemj.org/content/280/3/791
*  Suramin in Autism Treatment
You are here: Home / Archives for Suramin in Autism Treatment. Researchers Studying Century-Old Drug in Potential New Approach ... Suramin inhibits the binding of ATP and similar molecules to key purinergic receptors, according to Naviaux. It silences the ... Suramin works by inhibiting the signaling function of adenosine triphosphate (ATP), a nucleotide or small molecule produced by ... Low-dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial ...
  http://www.gordonmedical.com/unravelling-complex-chronic-illness/tag/suramin-in-autism-treatment/
*  Combination Chemotherapy With Suramin Plus Doxorubicin in Treating Patients With Advanced Solid Tumors
Patients receive suramin IV daily. over 1-2 hours on days 1-4 followed by doxorubicin IV over 10-15 minutes on day 5. Treatment ... A Phase I Trial of Suramin With Sequential Doxorubicin in Patients With Advanced Solid Tumors. Trial Phase:. Phase 1. Minimum ... courses of doxorubicin IV on day 1 every 4 weeks (courses 4, 6, 8, etc.) and suramin with. doxorubicin (courses 5, 7, 9 etc.) ... Describe the toxic effects of suramin with. sequential doses of doxorubicin in these patients. III. Assess the development of ...
  http://www.knowcancer.com/cancer-trials/NCT00003038/
*  Suramin - Wikipedia
Suramin was studied as a possible treatment for prostate cancer in a clinical trial. Suramin has been studied in a mouse model ... Suramin can also cause loss of appetite and irritability. Suramin causes non-harmful changes in urine during use, specifically ... Suramin is not extensively metabolized and about 80% is eliminated via the kidneys. The molecular formula of suramin is ... Suramin bound to proteins in the PDB Suramin, drug information by JBC Online National Cancer Institute Pharmacy and ...
  https://en.wikipedia.org/wiki/Suramin
*  Cell surface binding and cellular internalization properties of suramin, a novel antineoplastic agent. | Clinical Cancer...
We have attempted to address this problem by studying the cellular pharmacology of tritiated suramin ([3H]suramin) in the DU145 ... Cell surface binding and cellular internalization properties of suramin, a novel antineoplastic agent.. C A Stein, T M Khan, Z ... Although suramin has shown promise in preliminary clinical trials as an antineoplastic agent, it is unclear if its mode of ... Use of this competitor allowed us to determine that [3H]suramin bound to the surface of HL60 cells was internalized via the ...
  http://clincancerres.aacrjournals.org/content/1/5/509
*  Suramin, Paclitaxel, and Carboplatin in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer - Full Text...
Experimental: Treatment (suramin, paclitaxel, carboplatin) Patients receive suramin IV over 30 minutes on days 1 and 2. ... Suramin, Paclitaxel, and Carboplatin in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer. The safety ... Drug: suramin Drug: carboplatin Drug: paclitaxel Other: pharmacological study Other: laboratory biomarker analysis Phase 2 ... Patients receive suramin IV over 30 minutes on days 1 and 2. Patients also receive paclitaxel IV over 3 hours and carboplatin ...
  https://clinicaltrials.gov/show/NCT00006929
*  Suramin in Treating Patients With Refractory or Relapsed Multiple Myeloma or Castleman's Disease - Full Text View -...
OUTLINE: Patients receive suramin on days 1-5, 8, 11, 15, 19, 22, and 29. During course 1, patients also receive suramin on ... Suramin in Treating Patients With Refractory or Relapsed Multiple Myeloma or Castleman's Disease. The safety and scientific ... Suramin is administered IV over 2 hours on day 1 of course 1 and over 1 hour on all subsequent infusion days. Patients undergo ... Suramin. Antinematodal Agents. Anthelmintics. Antiparasitic Agents. Anti-Infective Agents. Antineoplastic Agents. Trypanocidal ...
  https://clinicaltrials.gov/ct2/show/NCT00002652
*  Suramin and radiotherapy in newly diagnosed glioblastoma: phase 2 NABTT CNS Consortium study. | Kennedy Krieger Institute
Patients received suramin by a conventional intermittent fixed-dosing regimen for 1 week prior to and during cranial RT (60 Gy ... Suramin is a polysulfonated naphthylurea that inhibits the function of growth factors and growth factor receptors implicated in ... Administration of suramin using an intermittent fixed-dosing regimen during cranial RT was generally well tolerated. However, ... Suramin and radiotherapy in newly diagnosed glioblastoma: phase 2 NABTT CNS Consortium study. ...
  https://www.kennedykrieger.org/node/89801
*  Suramin hexasodium salt| Abcam中国
购买Abcam Suramin hexasodium salt (CAS 129-46-4) (ab120422),纯度, 99%,分子式C51H34N6Na6O23S6,Non-selective P2 purinergic拮抗剂。1篇文献引用, ... Suramin promotes proliferation and scattering of renal epithelial cells.. J Pharmacol Exp Ther 314:383-90 (2005). Read more ( ... Prevention of muscle fibrosis and myonecrosis in mdx mice by suramin, a TGF-ß1 blocker.. Muscle Nerve 43:82-7 (2011). Read more ... Divergent effects of the purinoceptor antagonists suramin and pyridoxal-5'-phosphate-6-(2'-naphthylazo-6'-nitro-4',8'- ...
  http://www.abcam.cn/suramin-hexasodium-salt-ab120422.html
*  Suramin reverses autism in mice - AutismWeb Forum
Also, suramin is pretty toxic, so I would not be rushing to put my child into a study of something that doesn't last long and ... Suramin reverses autism in mice. Discuss autism theories, media stories, and efforts to put ASD on the government agenda here. ... To me , it isn't Suramin that is promising, but the primary research and hypothesis testing behind it as well as APT therapy in ... The author had published the suramin study (reversing ASD in MIA mouse model) before, so this is detailed follow up analysis ...
  http://www.autismweb.org/forum/viewtopic.php?f=6&t=32423&p=219848
*  COA of Suramin sodium salt | Certificate of Analysis | AbMole BioScience
View our Suramin sodium salt specific physical and chemical properties, and analytical data. ... COA of Suramin sodium salt contains the actual results obtained from testing performed as part of quality control. ... Suramin sodium salt is a polysulfonated naphthylurea that inhibits the binding of calmodulin to recognition sites on the ...
  http://www.abmole.com/literature/suramin-sodium-salt-coa.html
*  CACHE . Suramin Selectively Inhibits Inducible Nitric Oxide Synthase at the Calmodulin Binding Site . Kalamazoo College
Suramin Selectively Inhibits Inducible Nitric Oxide Synthase at the Calmodulin Binding Site. ... This study further investigates the nature of nNOS and iNOS inhibition by suramin by testing it in the presence of CaM with ... Moreover, western analyses of nNOS and iNOS in the presence of all three CaM variations indicated that suramin disrupts NOS-CaM ... These data suggest that suramin selectively inhibits iNOS over nNOS and that inhibition occurs by way of competition for the ...
  https://cache.kzoo.edu/handle/10920/31947
*  The approved pediatric drug suramin identified as a clinical candidate for the treatment of EV71 infection-suramin inhibits...
The approved pediatric drug suramin identified as a clinical candidate for the treatment of EV71 infection-suramin inhibits ... Moreover, we demonstrate that when suramin is used in vivo at doses equivalent to or lower than the highest dose already used ... Thus, suramin inhibits EV71 infection by neutralizing virus particles prior to cell attachment. Consequently, these findings ... Using a multidisciplinary approach, we found that the approved pediatric antiparasitic drug suramin blocked EV71 infectivity by ...
  https://research-repository.griffith.edu.au/handle/10072/65629
*  Repositorio da Producao Cientifica e Intelectual da Unicamp: Suramin affects metalloproteinase-9 activity and increases beta...
Results: We found that suramin affects metalloproteinase-9 activity and increases beta-dystroglycan. Furthermore, suramin also ... Suramin affects metalloproteinase-9 activity and increases beta-dystroglycan levels in the diaphragm of the dystrophin- ... Previously, we demonstrated that the anti-fibrotic agent suramin was effective in decreasing fibrosis in mdx muscles. In this ... Conclusions: These results show the potential benefits of suramin in maintaining the structure of the dystrophin-glycoprotein ...
  http://repositorio.unicamp.br/jspui/handle/REPOSIP/74845
*  1y8e - Proteopedia, life in 3D
The larger than anticipated flexibility of suramin manifested in this structure, and other details of VCP-suramin interactions ... Suramin is a competitive inhibitor of heparin binding to many proteins, including viral envelope proteins, protein tyrosine ... We report the structure of suramin, in complex with the heparin-binding site of vaccinia virus complement control protein (VCP ... Although it has shown clinical promise in treatment of several cancers, suramin has many undesirable side effects. There is ...
  http://proteopedia.org/wiki/index.php/1y8e
*  Wiebke Arlt - Mendeley
WORKSHOP ON SURAMIN WITH EMPHASIS ON PROSTATE-CANCER - REEVALUATION OF RESPONSE CRITERIA. *VANRIJSWIJK R ... ADRENOCORTICAL INSUFFICIENCY IN RHODESIAN SLEEPING SICKNESS IS NOT ATTRIBUTABLE TO SURAMIN. *HEPPNER C ...
  https://www.mendeley.com/profiles/wiebke-arlt/
*  Patent US8888810 - Compound barb medical device and method - Google Patentsuche
Suramin; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Plasminogen Activator Inhibitor-1; ...
  http://www.google.de/patents/US8888810
*  A Phase I Evaluation of Azidothymidine (AZT) in Children With Acquired Immune Deficiency Syndrome (AIDS) or AIDS Related...
The study is designed to test the drug zidovudine (AZT) in children, including study of drug levels in various parts of the body fluids, safety of the drug, and its effect on different parts of the body.. The effects of any drug, the way a drug enters the bloodstream, the way it is used by the body, and the way the body eliminates the drug may be very different in children compared with adults. The largest group of children who have AIDS are those who are less than 2 years of age. AIDS is often first identified in infants who are about 6 months old. Studies of AZT show that it might be useful in the treatment of AIDS. Thus it is important to study the effects of the drug in children. ...
  https://clinicaltrials.gov/show/NCT00000701?order=183
*  Search of: 'Adrenocortical carcinoma' - List Results - ClinicalTrials.gov
S9427, Suramin in Treating Patients With Stage III or Stage IV Adrenocortical Cancer Incurable by Surgery. *Adrenocortical ... Combination Chemotherapy With Suramin Plus Doxorubicin in Treating Patients With Advanced Solid Tumors. *Adrenocortical ...
  https://clinicaltrials.gov/ct2/results?cond=%22Adrenocortical+carcinoma%22

(1/824) Effects of heptanol on the neurogenic and myogenic contractions of the guinea-pig vas deferens.

1. The effects of the putative gap junction uncoupler, 1-heptanol, on the neurogenic and myogenic contractile responses of guinea-pig vas deferens were studied in vitro. 2. Superfusion of 2.0 mM heptanol for 20-30 min produced the following reversible changes in the biphasic neurogenic contractile response (8 trials): (i) suppression of both phases; (ii) delayed development of both the first as well as the second phase, accompanied by complete temporal separation of the two phases; (iii) prominent oscillations of force during the second (noradrenergic) phase only. 3. To eliminate prejunctional effects of heptanol, myogenic contractions were evoked by field stimulation of the vas in the presence of suramin (200 microM) and prazosin (1 microM). Heptanol (2.0 mM) abolished these contractions reversibly. 4. These results show that (i) heptanol inhibits both excitatory junction potential (EJP)-dependent and non EJP-dependent contractions of the vas; (ii) a postjunctional site of action of heptanol, probably intercellular uncoupling of smooth muscle cells, contributes to the inhibition of contraction.  (+info)

(2/824) Suramin and suramin analogs activate skeletal muscle ryanodine receptor via a calmodulin binding site.

Contraction of skeletal muscle is triggered by the rapid release of Ca2+ from the sarcoplasmic reticulum via the ryanodine receptor/calcium-release channel. The trypanocidal drug suramin is an efficient activator of the ryanodine receptor. Here, we used high-affinity [3H]ryanodine binding to sarcoplasmic reticulum from rabbit skeletal muscle to screen for more potent analogs of suramin. This approach resulted in the identification of NF307, which accelerates the association rate of [3H]ryanodine binding with an EC50 = 91 +/- 7 microM at 0.19 microM calculated free Ca2+. In single-channel recordings with the purified ryanodine receptor, NF307 increased mean open probability at 0.6 microM Ca2+ from 0.020 +/- 0.006 to 0.53 +/- 0.07 with no effect on current amplitude and unitary conductance. Like caffeine, NF307 exerts a very pronounced Ca2+-sensitizing effect (EC50 of Ca2+ shifted approximately 10-fold by saturating NF307 concentrations). Conversely, increasing concentrations of free Ca2+ sensitized the receptor for NF307 (EC50 = 14.6 +/- 3.5 microM at 0.82 microM estimated free Ca2+). The effects of NF307 and caffeine on [3H]ryanodine binding were additive, irrespective of the Ca2+ concentration. In contrast, the effects of calmodulin, which activates and inhibits the ryanodine receptor in the absence and presence of Ca2+, respectively, and of NF307 were mutually antagonistic. If the purified ryanodine receptor was prebound to a calmodulin-Sepharose matrix, 100 microM NF307 and 300 microM suramin eluted the purified ryanodine receptor to an extent that was comparable to the effect of 10 microM calmodulin. We conclude that NF307 and suramin interact directly with a calmodulin binding domain of the ryanodine receptor. Because of its potent calcium-sensitizing effect, NF307 may represent a lead compound in the search of synthetic ryanodine receptor ligands.  (+info)

(3/824) Regulation of gelatinase B production in corneal cells is independent of autocrine IL-1alpha.

PURPOSE: The matrix metalloproteinase gelatinase B is synthesized by cells at the leading edge of the corneal epithelium migrating to heal a wound. Recent data from the authors' laboratory suggest that excessive synthesis contributes to repair defects. The goal of the study reported here was to investigate mechanisms controlling gelatinase B production by corneal epithelial cells. METHODS: Freshly isolated cultures of corneal epithelial cells and early passage stromal fibroblasts from rabbit were used for these studies. RESULTS: In a previous study, it was found that the cytokine interleukin (IL)-1alpha is released into the culture medium of corneal epithelial cells more efficiently when they are plated at low density with limited cell-cell contact than when plated at high density. In this study, we show that production of gelatinase B by these cells is similarly affected by cell plating density. However, it is further demonstrated that these two events are not dependent on one another but occur in parallel: IL-1alpha does not regulate gelatinase B production (synthesis), nor was there evidence that any other secreted autocrine cytokine acts as mediator. Instead, our data suggest that gelatinase B production is downregulated directly by high cell density and indicate a connection to the level of protein kinase C activity. Nevertheless, the anticancer agent suramin, which blocks collagenase synthesis by interfering with autocrine cytokine-receptor interactions, still inhibits synthesis of gelatinase B. CONCLUSIONS: Unlike collagenase synthesis by corneal stromal fibroblasts, production (synthesis) of gelatinase B does not appear to be controlled by secreted autocrine cytokines but can still be inhibited by suramin. Suramin may make an effective therapeutic agent for controlling pathologic overproduction of gelatinase B in corneal ulcers.  (+info)

(4/824) Local regulation of vasopressin and oxytocin secretion by extracellular ATP in the isolated posterior lobe of the rat hypophysis.

It is now widely accepted that ATP functions as a signalling substance in the nervous system. The presence of P2 receptors mediating the action of extracellular ATP in brain regions involved in hormonal regulation raises the possibility that a similar role for ATP might also exist in the neuroendocrine system. In this study, the release from the rat isolated neurohypophysis preparation of endogenous ATP, oxytocin and vasopressin (AVP) were measured simultaneously using luciferin-luciferase and RIA techniques. After 70 min preperfusion, electrical field stimulation caused a rapid increase in the amount of ATP in the effluent and the release of AVP and oxytocin also increased stimulation-dependently. Inhibition of voltage-dependent Na+ channels by tetrodotoxin (1 microM) reduced the stimulation-evoked release of AVP and oxytocin; however, the evoked release of ATP remained unaffected. The effect of endogenous ATP on the hormone secretion was tested by suramin (300 microM), the P2 receptor antagonist. Suramin significantly increased the release of AVP, and the release of oxytocin was also enhanced. ATP, when applied to the superfusing medium, decreased the release of AVP, but not that of oxytocin, and its effect was prevented by suramin. ATP (60 nmol), added to the tissues, was readily decomposed to ADP, AMP and adenosine measured by HPLC combined with ultraviolet light detection, and the kinetic parameters of the enzymes responsible for inactivation of ATP (ectoATPase and ecto5'-nucleotidase) were also determined (Km=264+/-2.7 and 334+/-165 microM and vmax=6.7+/-1.1 and 2.54+/-0.24 nmol/min per preparation (n=3) for ectoATPase and ecto5'-nucleotidase respectively). Taken together, our data demonstrate the stimulation-dependent release, P2 receptor-mediated action and extracellular metabolism of endogenous ATP in the posterior lobe of the hypophysis and indicate its role, as a paracrine regulator, in the local control of hormone secretion.  (+info)

(5/824) Antioxidants improve impaired insulin-mediated glucose uptake and prevent migration and proliferation of cultured rabbit coronary smooth muscle cells induced by high glucose.

BACKGROUND: To explore the role of intracellular oxidative stress in high glucose-induced atherogenesis, we examined the effect of probucol and/or alpha-tocopherol on the migration and growth characteristics of cultured rabbit coronary vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: Chronic high-glucose-medium (22. 2 mmol/L) treatment increased platelet-derived growth factor (PDGF)-BB-mediated VSMC migration, [3H]thymidine incorporation, and cell number compared with VSMCs treated with normal-glucose medium (5.6 mmol/L+16.6 mmol/L mannose). Probucol and alpha-tocopherol significantly suppressed high glucose-induced increase in VSMC migration, cell number, and [3H]thymidine incorporation. Probucol and alpha-tocopherol suppressed high glucose-induced elevation of the cytosolic ratio of NADH/NAD+, phospholipase D, and membrane-bound protein kinase C activation. Probucol, alpha-tocopherol, and calphostin C improved the high glucose-induced suppression of insulin-mediated [3H]deoxyglucose uptake. Chronic high-glucose treatment increased the oxidative stress, which was significantly suppressed by probucol, alpha-tocopherol, suramin, and calphostin C. CONCLUSIONS: These findings suggest that probucol and alpha-tocopherol may suppress high glucose-induced VSMC migration and proliferation via suppression of increases in the cytosolic ratio of free NADH/NAD+, phospholipase D, and protein kinase C activation induced by high glucose, which result in reduction in intracellular oxidative stress.  (+info)

(6/824) Cell surface retention sequence binding protein-1 interacts with the v-sis gene product and platelet-derived growth factor beta-type receptor in simian sarcoma virus-transformed cells.

The cell surface retention sequence (CRS) binding protein-1 (CRSBP-1) is a newly identified membrane glycoprotein which is hypothesized to be responsible for cell surface retention of the oncogene v-sis and c-sis gene products and other secretory proteins containing CRSs. In simian sarcoma virus-transformed NIH 3T3 cells (SSV-NIH 3T3 cells), a fraction of CRSBP-1 was demonstrated at the cell surface and underwent internalization/recycling as revealed by cell surface 125I labeling and its resistance/sensitivity to trypsin digestion. However, the majority of CRSBP-1 was localized in intracellular compartments as evidenced by the resistance of most of the 35S-metabolically labeled CRSBP-1 to trypsin digestion, and by indirect immunofluorescent staining. CRSBP-1 appeared to form complexes with proteolytically processed forms (generated at and/or after the trans-Golgi network) of the v-sis gene product and with a approximately 140-kDa proteolytically cleaved form of the platelet-derived growth factor (PDGF) beta-type receptor, as demonstrated by metabolic labeling and co-immunoprecipitation. CRSBP-1, like the v-sis gene product and PDGF beta-type receptor, underwent rapid turnover which was blocked in the presence of 100 microM suramin. In normal and other transformed NIH 3T3 cells, CRSBP-1 was relatively stable and did not undergo rapid turnover and internalization/recycling at the cell surface. These results suggest that in SSV-NIH 3T3 cells, CRSBP-1 interacts with and forms ternary and binary complexes with the newly synthesized v-sis gene product and PDGF beta-type receptor at the trans-Golgi network and that the stable binary (CRSBP-1.v-sis gene product) complex is transported to the cell surface where it presents the v-sis gene product to unoccupied PDGF beta-type receptors during internalization/recycling.  (+info)

(7/824) Modulation of ATP-responses at recombinant rP2X4 receptors by extracellular pH and zinc.

The modulatory effects of extracellular H+ and Zn2+ were tested against ATP-responses at rat P2X4 (rP2X4) receptors expressed in Xenopus oocytes under voltage-clamp conditions. ATP (0.1-100 microM, at pH 7.5), evoked inward currents via rP2X4 receptors (EC50 value, 4.1+/-0.98 microM; nH, 1.2+/-0.1). ATP potency was reduced 2 fold, at pH 6.5, without altering maximal activity. ATP potency was reduced by a further 4 fold, at pH 5.5, and the maximal activity of ATP was also reduced. Alkaline conditions (pH 8.0) had no effect on ATP-responses. Zn2+ (100 nM - 10 microM) potentiated ATP-responses at the rP2X4 receptor by 2 fold, whereas higher concentrations (30 microM - 1 mM) inhibited ATP-responses. Zn2+ potentiation was due to an increase in ATP potency, whereas its inhibitory action was due to a reduction in ATP efficacy. Zn2+ modulation of ATP-responses was pH-dependent. At pH 6.5, the bell-shaped curve for Zn2+ was shifted to the right by 1 log unit. At pH 5.5, Zn2+ potentiation was abolished and its inhibitory effect reduced considerably. Suramin (50 microM) also potentiated ATP-responses at rP2X4 receptors. Neither H+ (pH 6.5 and 5.5), Zn2+ (10-100 microM) or a combination of both failed to reveal an inhibitory action of suramin at rP2X4 receptors. In conclusion, H+ and Zn2+ exerted opposite effects on the rP2X4 receptor by lowering and raising agonist potency, respectively. H+ (> or = 3 microM) and Zn2+ (> or = 30 microM) also reduces agonist efficacy by lowering the number of rP2X4 receptors available for activation. The striking differences between the modulatory actions of H+ and Zn2+ at rP2X4 and rP2X2 receptors are discussed.  (+info)

(8/824) Neural modulation of the cyclic electrical and mechanical activity in the rat colonic circular muscle: putative role of ATP and NO.

1. The rat colonic circular muscle displays cyclic episodes of myenteric potential oscillations (MPOs), each of them associated with a spontaneous contraction. Nifedipine 1 microM abolished both MPOs and their associated contractions. TTX (1 microM) increased the amplitude and frequency of spontaneous contractions. 2. Electrical field stimulation (EFS) induced a non-adrenergic non-cholinergic (NANC) inhibitory junction potential (IJP), with two phases: an initial fast hyperpolarization (characterized by IJP amplitude) and a sustained hyperpolarization (characterized by IJP duration). 3. Sodium nitroprusside (10 microM) hyperpolarized and abolished spontaneous contractions even in presence of TTX or 1 microM apamin. ATP (100 microM) also hyperpolarized and abolished spontaneous contractions but its effects were decreased by TTX and abolished by apamin. 4. Suramin (100 microM) or apamin reduced the amplitude of the IJPs, but did not affect their duration. Incubation with L-NOARG (1 mM) reduced the duration but not the amplitude of the IJPs. In presence of L-NOARG plus suramin or L-NOARG plus apamin, both duration and amplitude of the IJPs were reduced but a residual IJP could still be recorded. 5. We conclude that the mechanical and electrical cyclic activity of the rat colonic circular muscle is modulated but not originated by the enteric nervous system and involves L-type calcium channel activity. EFS induces release of NANC inhibitory neurotransmitters which hyperpolarize and relax smooth muscle cells. Both ATP and NO are involved in IJP generation: ATP is responsible for the first phase of the IJPs involving activation of apamin-sensitive potassium channels, whereas NO initiates the second phase which is independent of the activation of such channels.  (+info)



  • mechanism of act
  • Using a multidisciplinary approach, we found that the approved pediatric antiparasitic drug suramin blocked EV71 infectivity by a novel mechanism of action that involves binding of the naphtalentrisulonic acid group of suramin to the viral capsid. (edu.au)
  • drug
  • The dynamics of internalization and compartmentalization of suramin in DU145 revealed that within a narrow concentration range, internalization was dependent on time of exposure and drug concentration. (aacrjournals.org)
  • toxic
  • Also, suramin is pretty toxic, so I would not be rushing to put my child into a study of something that doesn't last long and has the potential to harm. (autismweb.org)
  • Bayer
  • The formula of suramin was kept secret by Bayer for commercial reasons, however, it was elucidated and published in 1924 by Ernest Fourneau and his team of the Pasteur Institute. (wikipedia.org)
  • functional
  • Suramin contains six aromatic systems - four benzene rings, sandwiched by a pair of naphthalene moieties - plus four amide functional groups (in addition to the urea) and six sulfonic acid groups. (wikipedia.org)
  • In this study, we were interested to see whether suramin could affect metalloproteinases (MMP) and improve the functional activity of the mdx diaphragm muscle. (unicamp.br)
  • study
  • The author had published the suramin study (reversing ASD in MIA mouse model) before, so this is detailed follow up analysis using suramin on the same mouse model. (autismweb.org)
  • involvement
  • In African trypanosomiasis it is used for early disease before central nervous system involvement, as a second line option to suramin. (wikipedia.org)
  • potential
  • Conclusions: These results show the potential benefits of suramin in maintaining the structure of the dystrophin-glycoprotein complex. (unicamp.br)
  • structure
  • We report the structure of suramin, in complex with the heparin-binding site of vaccinia virus complement control protein (VCP), which interacts with heparin in a geometrically similar manner to many FGFs. (proteopedia.org)
  • plasma
  • Suramin does not distribute well into cerebral spinal fluid and its concentration in the tissues is equivalently lower than its concentration in the plasma. (wikipedia.org)
  • Analysis
  • Kinetic analysis demonstrated that the half-maximal inhibitory constant, IC50, of suramin for iNOS with wild type CaM was 2.6 uM and 41 uM, in the presence and absence of 1. (kzoo.edu)
  • cell
  • Suramin works by inhibiting the signaling function of adenosine triphosphate (ATP), a nucleotide or small molecule produced by cellular mitochondria and released from the cell as a danger signal. (gordonmedical.com)
  • The binding of [3H]suramin to the cell surface was competitive with respect to a phosphorothioate oligodeoxynucleotide homopolymer of cytidine, 28 bases in length, but was not affected by ATP. (aacrjournals.org)