TY  - JOUR
AB  - Rheumatoid arthritis is a hyperactive immune disorder that results in severe inflammation in synovial joints, cartilage, and bone deterioration, resulting in immobilization of joints. Traditional approaches for the treatment of rheumatoid arthritis are associated with some limiting factors such as suboptimal patient compliance, inability to control the progression of disorder, and safety concerns. Therefore, innovative drug delivery carriers for efficient therapeutic delivery at inflamed synovial sites with better safety assessment are urgently needed to address these issues. From this perspective, nanotechnology is an outstanding alternative to traditional drug delivery approaches, and it has shown great promise in developing novel carriers to treat rheumatoid arthritis. Considering the current research and future application of nanocarriers, it is believed that nanocarriers can be a crucial element in rheumatoid arthritis treatment. This paper covers all currently available pathophysiological aspects of rheumatoid arthritis and treatment options. Future research for the reduction of synovial inflammation should focus on developing multifunction nanoparticles capable of delivering therapeutic agents with improved safety, efficacy, and cost-effectiveness to be commercialized.
AU  - Rani, R.*
AU  - Raina, N.*
AU  - Sharma, A.*
AU  - Kumar, P.
AU  - Tulli, H.S.*
AU  - Gupta, M.*
C1  - 67812
C2  - 54290
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 2287-2310
TI  - Advancement in nanotechnology for treatment of rheumatoid arthritis: Scope and potential applications.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 396
IS  - 10
PB  - Springer
PY  - 2023
SN  - 0028-1298
ER  - 

TY  - JOUR
AB  - HMG-CoA-Reductase inhibitors (HMGRIs) are currently the most widely used group of drugs in patients with coronary artery disease (CAD) and are given preemptively to patients with high levels of cholesterol, including those with diabetes mellitus (DM). However, intake of HMGRIs also increases the progression of coronary artery calcification (CAC) and the risk of developing DM. This study aimed to investigate whether HMGRI intake interacts with the diabetes-associated genetic risk score (GRS) to affect CAC progression using data from the population-based Heinz Nixdorf Recall (HNR) study. CAC was measured in 3157 participants using electron-beam computed tomography twice, at baseline (CACb) and 5 years later (CAC5y). CAC progression was classified as slow, expected, or rapid based on predicted values. Weighted DM GRS was constructed using 100 diabetes mellitus-associated single nucleotide polymorphisms (SNPs). We used log-linear regression to evaluate the interaction of HMGRI intake with diabetes-associated GRS and individual SNPs on CAC progression (rapid vs. expected/slow), adjusting for age, sex, and log(CACb + 1). The prevalence of rapid CAC progression in the HNR study was 19.6%. We did not observe any association of the weighted diabetes mellitus GRS with the rapid progression of CAC (relative risk (RR) [95% confidence interval (95% CI)]: 1.01 [0.94; 1.10]). Furthermore, no indication of an interaction between GRS and HMGRI intake was observed (1.08 [0.83; 1.41]). Our analyses showed no indication that the impact of HMGRIs on CAC progression is significantly more severe in patients with a high genetic risk of developing DM than in those with a low GRS.
AU  - Pechlivanis, S.
AU  - Jung, J.*
AU  - Moebus, S.*
AU  - Lehmann, N.*
AU  - Mahabadi, A.A.*
AU  - Hoffmann, P.*
AU  - Erbel, R.*
AU  - Nöthen, M.M.*
AU  - Bachmann, H.S.*
C1  - 62084
C2  - 50639
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 1713-1725
TI  - Pharmacogenetic association of diabetes-associated genetic risk score with rapid progression of coronary artery calcification following treatment with HMG-CoA-reductase inhibitors -results of the Heinz Nixdorf Recall Study.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 394
IS  - 4
PB  - Springer
PY  - 2021
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Ahles, A.*
AU  - Hinz, L.*
AU  - Herrmann, J.*
AU  - Meunier, S.*
AU  - Feederle, R.
AU  - Milting, H.*
AU  - Engelhardt, S.*
C1  - 58557
C2  - 48175
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 33-33
TI  - Monitoring betal-adrenoceptor phosphorylation in human heart.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 393
IS  - SUPPL 1
PB  - Springer
PY  - 2020
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Rajan, S.*
AU  - Weber, J.*
AU  - Chao, Y.K.*
AU  - Kannler, M.*
AU  - Krasteva-Christ, G.*
AU  - Yildirim, A.Ö.
AU  - Brosien, M.*
AU  - Schredelseker, J.*
AU  - Weissmann, N.*
AU  - Grimm, C.*
AU  - Gudermann, T.*
AU  - Dietrich, A.*
C1  - 58558
C2  - 48174
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 37-37
TI  - Essential functions of TRPV4 channels in alveolar epithelium.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 393
IS  - SUPPL 1
PB  - Springer
PY  - 2020
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Sander, P.*
AU  - Arduino, D.M.
AU  - Wilting, F.*
AU  - Schweitzer, M.*
AU  - Gudermann, T.*
AU  - Perocchi, F.
AU  - Schredelseker, J.*
C1  - 58556
C2  - 48176
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 18-19
TI  - Novel mitochondrial Ca2+ enhancers for the treatment of cardiac arrhythmia.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 393
IS  - SUPPL 1
PB  - Springer
PY  - 2020
SN  - 0028-1298
ER  - 

TY  - JOUR
AB  - The effects of 100 mu M of 3 ',5 '-cGMP, cAMP, cCMP, and cUMP as well as of the corresponding membrane-permeant acetoxymethyl esters on anti-CD3-antibody (OKT3)-induced IL-2 production of HuT-78 cutaneous T cell lymphoma (Sezary lymphoma) cells were analyzed. Only 3 ',5 '-cGMP significantly reduced IL-2 production. Flow cytometric analysis of apoptotic (propidium iodide/annexin V staining) and anti-proliferative (CFSE staining) effects revealed that 3 ',5 '-cGMP concentrations > 50 mu M strongly inhibited proliferation and promoted apoptosis of HuT-78 cells (cultured in the presence of alpha CD3 antibody). Similar effects were observed for the positional isomer 2 ',3 '-cGMP and for 2 ',-GMP, 3 '-GMP, 5 '-GMP, and guanosine. By contrast, guanosine and guanosine-derived nucleotides had no cytotoxic effect on peripheral blood mononuclear cells (PBMCs) or acute lymphocytic leukemia (ALL) xenograft cells. The anti-proliferative and apoptotic effects of guanosine and guanosine-derived compounds on HuT-78 cells were completely eliminated by the nucleoside transport inhibitor NBMPR (S-(4-Nitrobenzyl)-6-thioinosine). By contrast, the ecto-phosphodiesterase inhibitor DPSPX (1,3-dipropyl-8-sulfophenylxanthine) and the CD73 ecto-5 '-nucleotidase inhibitor AMP-CP (adenosine 5 '-(alpha,beta-methylene)diphosphate) were not protective. We hypothesize that HuT-78 cells metabolize guanosine-derived nucleotides to guanosine by yet unknown mechanisms. Guanosine then enters the cells by an NBMPR-sensitive nucleoside transporter and exerts cytotoxic effects. This transporter may be ENT1 because NBMPR counteracted guanosine cytotoxicity in HuT-78 cells with nanomolar efficacy (IC50 of 25-30 nM). Future studies should further clarify the mechanism of the observed effects and address the question, whether guanosine or guanosine-derived nucleotides may serve as adjuvants in the therapy of cancers that express appropriate nucleoside transporters and are sensitive to established nucleoside-derived cytostatic drugs.
AU  - Schneider, E.H.*
AU  - Hofmeister, O.
AU  - Kälble, S.*
AU  - Seifert, R.*
C1  - 58978
C2  - 48564
CY  - One New York Plaza, Suite 4600, New York, Ny, United States
SP  - 1251–1267
TI  - Apoptotic and anti-proliferative effect of guanosine and guanosine derivatives in HuT-78 T lymphoma cells.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 393
PB  - Springer
PY  - 2020
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Khajavi, N.*
AU  - Finan, B.
AU  - Kluth, O.*
AU  - Müller, T.D.
AU  - Mergler, S.*
AU  - Schulz, A.*
AU  - Kleinau, G.*
AU  - Scheerer, P.*
AU  - Schuermann, A.*
AU  - Gudermann, T.*
AU  - Tschöp, M.H.
AU  - Krude, H.*
AU  - DiMarchi, R.D.*
AU  - Biebermann, H.*
C1  - 55551
C2  - 46203
CY  - 233 Spring St, New York, Ny 10013 Usa
SP  - S35-S35
TI  - Tri-agonist-induced PLC activation is associated with robust insulin secretion from murine islets.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 392
PB  - Springer
PY  - 2019
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Morgenstern, J.*
AU  - Volk, N.*
AU  - Schumacher, D.*
AU  - Oguchi, Y.*
AU  - Kopf, S.*
AU  - Groener, J.B.*
AU  - Nawroth, P.P.
AU  - Fleming, T.*
AU  - Freichel, M.*
C1  - 55549
C2  - 46205
CY  - 233 Spring St, New York, Ny 10013 Usa
SP  - S39-S39
TI  - Compensatory mechanisms for methylglyoxal detoxification in experimental & clinical diabetes.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 392
PB  - Springer
PY  - 2019
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Zischka, H.
C1  - 55550
C2  - 46204
CY  - 233 Spring St, New York, Ny 10013 Usa
SP  - S3-S3
TI  - Mitochondrial toxicology: Rescuing mitochondria in Wilson disease avoids acute liver failure.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 392
PB  - Springer
PY  - 2019
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Hofmann, K.*
AU  - Vierkotten, S.
AU  - Gudermann, T.*
AU  - Yildirim, A.Ö.
AU  - Königshoff, M.
AU  - Dietrich, A.*
C1  - 46780
C2  - 37818
CY  - New York
SP  - S18
TI  - Dissecting the role of TRPC6-channels in bleomycin-induced pulmonary fibrosis.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 388
PB  - Springer
PY  - 2015
SN  - 0028-1298
ER  - 

TY  - JOUR
AB  - Upon activation, microglia, the immunocompetent cells in the brain, get highly phagocytic and release pro-inflammatory mediators like nitric oxide (NO). Excessive NO production is pivotal in neurodegenerative disorders, and there is evidence that abnormalities in NO production and inflammatory responses may at least support a range of neuropsychiatric disorders, including depression. Although extracts of St. John's wort (Hypericum perforatum L.) have been used for centuries in traditional medicine, notably for the treatment of depression, there is still considerable lack in scientific knowledge about the impact on microglia. We used N11 and BV2 mouse microglia, as well as RAW 264.7 macrophages to investigate the effects of St. John's wort extract and constituents thereof on NO production Moreover, flow cytometry and fluorescence microscopy were employed to analyze the influence on phagocytosis, transcription factor activation states, and cell motility. We found that extracts of St. John's wort efficiently suppress lipopolysaccharide-induced NO release and identified hyperforin as the responsible compound, being effective at concentrations between 0.25 and 0.75 microM. The reduced NO production was mediated by diminished inducible nitric oxide synthase expression on the mRNA and protein level. In addition, at similar concentrations, hyperforin reduced zymosan phygocytosis to 20-40% and putatively acted by downregulating the CD206 macrophage mannose receptor and modulation of cell motility. We found that the observed effects correlate with a suppression of the activated state of Nf-kappaB and phospho-CREB, while c-JUN, STAT1, and HIF-1alpha activity and cyclooxygenase-2 expression remained unaffected by hyperforin. These results reveal that hyperforin influences pro-inflammatory and immunological responses of microglia that are involved in the progression of neuropathologic disorders.
AU  - Kraus, B.*
AU  - Wolff, H.
AU  - Elstner, E.F.*
AU  - Heilmann, J.*
C1  - 5952
C2  - 27640
SP  - 541-553
TI  - Hyperforin is a modulator of inducible nitric oxide synthase and phagocytosis in microglia and macrophages.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 381
IS  - 6
PB  - Springer
PY  - 2010
SN  - 0028-1298
ER  - 

TY  - JOUR
AB  - Background: In classrooms high concentrations of particulate matter PM10 were measured. This study addresses the hazard of indoor particles in comparison to the better studied outdoor particles. Methods: Samples were taken from six schools during teaching hours. Genome-wide gene expression in human BEAS-2B lung epithelial cells was analyzed and verified by quantitative PCR. Polycyclic aromatic hydrocarbons (PAH), endotoxin, and cat allergen Fel d 1 were analyzed with standard methods. Enhancement of allergic reactivity by PM10 was confirmed in human primary basophils. Acceleration of human blood coagulation was determined with supernatants of PM10-exposed human peripheral blood monocytes. Results: Indoor PM10 induced SERPINB2 (involved in blood coagulation) and inflammatory genes (like CXCL6, CXCL1, IL6, IL8, all p<0.001). Outdoor PM10 induced xenobiotic metabolizing enzymes (CYP1A1, CYP1B1, TIPARP, all p<0.001). The induction of inflammatory genes by indoor PM10 was explained by endotoxin (indoor 128.5±42.2EU/mg versus outdoor 13.4±21.5EU/mg, p<0.001), the induction of CYP by outdoor PAH (indoor 8.3±4.9ng/mg versus outdoor 16.7±15.2ng/mg, p<0.01). The induction of SERPINB2 was confirmed by a more rapid human blood coagulation (p<0.05). Indoor PM10 only affected allergic reactivity from human primary basophils from cat allergic individuals. This was explained by varying Fel d 1 concentrations in indoor PM10 (p<0.001). Conclusions: Indoor PM10, compared to outdoor PM10, was 6 times higher and on an equal weight basis induced more inflammatory and allergenic reactions, and accelerated blood coagulation. Outdoor PM10 had significantly lower effects, but induced detoxifying enzymes. Therefore, preliminary interventions for the reduction of classroom PM10 seem reasonable, perhaps by intensified ventilation.
AU  - Oeder, S.
AU  - Weichenmeier, I.
AU  - Schober, W.
AU  - Schierl, R.*
AU  - Dietrich, S.*
AU  - Fromme, H.*
AU  - Matuschek, G.
AU  - Behrendt, H.
AU  - Buters, J.T.M.
C1  - 32482
C2  - 35942
CY  - New York
SP  - 66
TI  - Differential induction of inflammatory and xenobiotic metabolizing genes by indoor and outdoor PM10.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 381
PB  - Springer
PY  - 2010
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Geuenich, S.
AU  - Haberl, C.
AU  - Egger, D.
AU  - Hültner, L.
AU  - Sagebiel, S.
AU  - Stötzer, O.
AU  - Wilmanns, W.
AU  - Denzlinger, C.
C1  - 20508
C2  - 13718
TI  - Pharmacologic Modulation of Leukotrine Production in Murine Mast Cells.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
PY  - 1993
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Neu, E.
AU  - Broers, D.
AU  - Michailov, M.C.
AU  - Hüting, D.
AU  - Magour, S.
C1  - 20095
C2  - 13270
TI  - Pathophysiological Electrical and Motor Reactions of Isolated Urinary Bladder Preparations (Guinea Pig) on Cypermethrin.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 345
PY  - 1992
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Rehse, K.
AU  - Kesselhut, A.
AU  - Schein, V.
AU  - Kämpfe, M.
AU  - Rose, B.
AU  - Unsöld, E.
C1  - 19220
C2  - 12291
SP  - 301-305
TI  - Antithrombotic Effect of Selected Oligoamines in Rats.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 324
PY  - 1991
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Hartmann, M.
AU  - Kessler, W.
C1  - 18370
C2  - 11563
TI  - Pharmacokinetics and Endogeneous Production of Isoprene in Humans.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
PY  - 1990
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Schwegler, U.
AU  - Jiang, X.
AU  - Kessler, W.
AU  - Johanson, G.
AU  - Filser, J.G.
C1  - 18371
C2  - 11564
TI  - Pharmakokinetik von Styrol bei Ratte und Maus und Bestimmung von Styrol-7,8-Oxid im Blut von Ratten.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
PY  - 1990
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Denk, B.
AU  - Oesterle, D.
AU  - Deml, E.
C1  - 17284
C2  - 10316
TI  - Induction of Foci by X-Rays and by Ethylene Oxide in a Rat Liver Foci Bioassey: Calculation of the Rad-Equivalence Factor of the Initiating Potency of a Physical and Chemical Carcinogen.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
PY  - 1988
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Filser, J.G.
AU  - Baumann, M.
C1  - 17781
C2  - 10692
SP  - S.66
TI  - Pharmacokinetics of 2-nitropropane in Rats and Determination of Enzymes in Serium Specific for Liver Injury.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 337 (Suppl.)
PY  - 1988
SN  - 0028-1298
ER  - 

TY  - JOUR
AB  - The functional size of different types of opiate receptors was determined in situ by the radiation inactivation technique. The Mr of opiate binding sites was estimated to be about 90,000 daltons; the data revealed no significant differences between the molecular sizes of either μ-, δ- or κ{script}-sites in rat brain membranes. An identical molecular size was found also for the δ-sites in the neuroblastoma x glioma hybrid cell clone, NG 108-15.
AU  - Ott, S.L.*
AU  - Costa, T.*
AU  - Hietel, B.
AU  - Schlegel, W.C.*
AU  - Wüster, M.*
C1  - 41760
C2  - 38481
SP  - 160-162
TI  - The molecular size of multiple opiate receptors.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 324
IS  - 2
PY  - 1983
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Andrae, U.
C1  - 41355
C2  - 40370
SP  - 49
TI  - Repair replication in isolated rat hepatocytes determined with the bromodeoxyuridine-CsCl-gradient method.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 316
IS  - Suppl.
PY  - 1981
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Schwarz, L.R.
AU  - Barth, C.A.
C1  - 41484
C2  - 38413
SP  - 28
TI  - Is there a biliary secretion in monolayer cultures of rat hepatocytes?.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 316
IS  - Suppl.
PY  - 1981
SN  - 0028-1298
ER  - 

TY  - JOUR
AU  - Seuss, H.
AU  - Ziegler-Skylakakis, K.
AU  - Zinner, H.
C1  - 40934
C2  - 38412
SP  - no. 165
TI  - Comparison of the inotropic and Na-pump inhibitory effects of AR-L 57[6-(2,4-dimethoxyphenyl)-imidazo-(4,5-β)-pyridine] and dihydro-ouabain.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 313
IS  - SUPPL.
PY  - 1980
SN  - 0028-1298
ER  - 

TY  - JOUR
AB  - 1. In the isolated papillary muscle of the guinea pig sodium fluoroacetate (FAc) produced, after an initial decrease in force of concentration, a transient positive inotropic effect which was due to an increase in the rate of force development. Time to peak force was shortened and relaxation time was prolonged whereas total contraction time was barely affected. Threshold and maximally effective concentrations for the positive inotropic effect were 1×10-5 and 5×10-3 M, respec tively. 2. Noradrenaline depletion by pretreatment of the animals with reserpine or β-adrenoceptor blockade with 5×10-6 M (±)-propranolol did not prevent the positive inotropic effect of 1×10-3 M FAc. 3. Reduction of [Na]0 from 140 to 70 mM (sucrose for osmotic adjustment) resulted in a decrease of the positive inotropic effect of 1×10-3 M FAc to about 54% of control, whereas a diminution of [K]0 from 9.6 to 2 mM caused a 4-fold increase. 4. The positive inotropic effect of 1×10-3 M FAc progressively increased when the stimulation frequency was increased from 0.064 to 0.5 Hz; rested-state contractions (0.004 Hz) were not increased by FAc. At a stimulation frequency of 2 Hz, FAc developed exclusively a negative inotropic effect which resulted in a contracture. 5. In the presence of ceveratrum alkaloids (0.8 μM veratridine or 30 nM germitrine), the positive inotropic effect of 1×10-3 M FAc was markedly augmented (about 5-fold). Tetrodotoxin (10 μM) prevented the enhancing effect of 0.8 μM veratridine on the positive inotropic effect of FAc. 6. At a low stimulation frequency (0.064 Hz), 1×10-3 M FAc prolonged the action potential duration of a guinea-pig papillary muscle within 2 h by 30%. At a stimulation rate of 1 Hz, a shortening of the action potential duration by 35% and a depolarization of the membrane resting potential by 4.3 mV occurred. 7. It is tentatively concluded that FAc like cardioactive steroids exerts its positive inotropic effect by an interference with the Na-extrusion mechanism thereby facilitating the Ca-uptake by an Na-Ca exchange.
AU  - Korth, M.
AU  - Weger, N.
AU  - Reiter, M.D.
C1  - 42007
C2  - 35800
SP  - 7-14
TI  - The positive inotropic action of sodium fluoroacetate on guinea-pig ventricular myocardium.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 303
IS  - 1
PY  - 1978
SN  - 0028-1298
ER  - 

TY  - JOUR
AB  - The cholestatic bile acid taurolithocholate inhibits taurocholate uptake by isolated liver cells non-competitively. Inhibition is instantaneous and inversely related to the cell number in the incubate. The Kiamounts to 7 μM in the presence of 2 mg cellular protein per ml. Secretion of taurocholate by isolated liver cells is not affected by taurolithocholate up to a concentration of 50 μM. This indicates a difference between the carrier for taurocholate uptake and the carrier for taurocholate secretion. Inhibition of bile acid uptake by liver cells may be involved in the pathogenesis of lithocholate-induced cholestasis.
AU  - Schwenk, M.
AU  - Schwarz, L.R.
AU  - Greim, H.A.
C1  - 40962
C2  - 38136
SP  - 175-179
TI  - Taurolithocholate inhibits taurocholate uptake by isolated hepatocytes at low concentrations.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 298
IS  - 2
PY  - 1977
SN  - 0028-1298
ER  - 

TY  - JOUR
AB  - The positive inotropic effect of noradrenaline on the guinea-pig papillary muscle is potentiated in the presence of 1×10-5 M tyramine, the concentration of noradrenaline that is necessary to produce a half maximal increase in force of contraction being reduced to about one third. There is no alteration of the maximal inotropic effect since the concentration-effect curve of noradrenaline is simply shifted to the left. In the presence of 3×10-3 M tyramine, which by itself increases contractility by a dual mechanism (an indirect sympathomimetic and a direct postsynaptic one which is not induced by stimulation of adrenergic β-receptors), noradrenaline (1×10-5 M) produces an additional inotropic effect leading to a force of contraction which surmounts the maximum of the normal concentration-effect curve of noradrenaline by about 30%. The "supramaximal" isometric contraction curve of the papillary muscle produced by the combined effects of 3×10-3 M tyramine and 1×10-5 M noradrenaline differs from the contraction curve in the presence of 1×10-5 M noradrenaline alone in having a steeper ascending slope and a slower relaxation phase. The mean velocity of force development (S1) exceeds the maximum value of the normal concentration-effect curve of noradrenaline by about 50%. There is no increase in the maximum of the mean velocity of relaxation (S2). The relaxation time of the supramaximal contraction curve as well as the duration of its action potential are the result of the opposing influences of the two substances, noradrenaline shortening and tyramine prolonging both action potential and relaxation time. © 1972 Springer-Verlag.
AU  - Brandt, W.
AU  - Reiter, M.
AU  - Seibel, K.
C1  - 41968
C2  - 0
SP  - 294-306
TI  - "Supramaximal" enhancement of the inotropic effect of noradrenaline by tyramine.
JO  - Naunyn-Schmiedebergs Arch. Pharmakol.
VL  - 273
IS  - 3
PY  - 1972
SN  - 0028-1298
ER  -